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Radly Balko reports on the war on prescription painkillers in the first of a three part series.

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Bad policy, driven by the war on drugs, has been affecting patient access to opioid medication the last few years and availability is becoming more unpredictable every year.

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“…drug control has taken priority over ensuring access to effective treatment….Police and prosecutors now dictate medical policy.”

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The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  

Welcome to my Weblog on Pain Management!

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 Three important new articles from March, August and November 2011, show ketamine acts on glia.

Emphasis within articles is mine.

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Microglia: a promising target for treating neuropathic and postoperative pain, and morphine tolerance.

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Girl with CRPS cold type two years, pain free on naltrexone 3 mg

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KR, 17 year old seen 11/4/11, with Complex Regional Pain Syndrome [CRPS] involving left lower limb from foot to hip, onset 3/09. She has nonspecific immune system abnormalities and many food sensitivities that caused leaky gut syndrome and 30 lb weight loss with certain foods causing the stomach to be rock hard and vomit. Elimination diet allowed her to regain 30 lbs.

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CRPS diagnosed February 2011, two years after first symptoms. The leg was cold, purple, mottled with allodynia. Pain had been 9 on scale of 10 for weeks prior to my visit when she was started on prednisone 60 mg x 1 week, 40 mg 1 week, and a few days on 20 mg, dropping her average pain to 4/10. Pain at my visit 11/4/11, ranged from 4 to 9, average 5, that was 40% better after prednisone. She takes a wheelchair to school and for distance, is able to walk short distances with cane, and without cane she concentrates walking slowly to avoid limp. She is very bright, highly motivated and described the limb as cold, aching, throbbing, shooting, stabbing, sharp, tender, burning, exhausting, tiring, miserable, unbearable. Pain severely interfered with walking, work, sleep, enjoyment of life, general activity, and relations with others. At rare times, the limb would jump. Numbness was present posteriorly off and on, especially when sitting, not present when standing.

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She had good health until mononucleosis at age 13 in October 2007. A few weeks later irritable bowel syndrome began (IBS-C), then CRPS began after injury March 2009, reinjury July 2009, then no problems until February 2011. The initial injury occurred when roughhousing with a friend, and her foot pulled her toes in a dorsiflexed position. The next day it was swollen and purple with bruising pain after the first injury. She was in a boot for several weeks. CRPS improved, she went to Peru climbing Machu Pichu when she was reinjured again. The foot was swollen, burning with allodynia. She was taken to a hospital in Chile where they wrapped the foot, advised to take Advil. Once home, she went to physical therapy. It resolved in 6 weeks.

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February 2011, fulfilling PE for high school, she tried out for swim team. Day two, she had pain from kicking in the water and was never able to get back into the water. She was in crutches the next 2.5 months and began physical therapy three times weekly since then. Pain began in the sole of the foot, but a slip and fall in the rain caused pain to spread to the hip. A flare in the past month caused pain much more in the left knee after prolonged sitting for tests. She now takes her wheelchair to school which she began to use early October 2011. She was in the chair consistently two weeks, now only as needed, and never uses it at home. She has used a cane since later April when she got off her crutches. In hot weather, the cold left lower limb sweats profusely. No hair changes. On prednisone, toes nails grow faster. She has used warm and cold compresses to relieve pain. She failed gabapentin when it caused her to be nonfunctional on 900 mg/day with no relief. Lyrica caused hives. Nortriptyline caused personality change, becoming very mean, an Atilla the Hun, opposite her usual good nature. Cymbalta 20 mg – severe dry throat, thick mucous, medications lodged in esophagus. Tried Tramadol 25 mg TID and Naproxen 500 bid.

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Incidentally, she saw a neurologist at Children’s Hospital in 2009 due to sudden onset of diplopia that was found due to allergy to contacts, and resolved with new contacts. She saw an allergist in 2010, and tested positive for nonspecific autoimmune disorder: ANA 1:160 speckled, positive for food sensitivities, and after four months of stopping certain foods, ANA was negative: gluten, dairy, garlic, broccoli, lima beans, banana, asparagus, pineapple, oyster, mushroom. While eating those foods she had IBS-C, stomach would harden, causing vomiting, and she lost 30 lbs, was 120 before —- it is part of the leaky gut syndrome that prevented her to absorb certain nutrients. She has regained weight and all symptoms resolved. She does not have dry mouth or dry eyes. She is sensitive to normal doses of medications like her grandmother.

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Exam: Toes are cold on the left. At the moment, no changes in hair, skin color, temperature, sweating. Stretch reflexes symmetrical, brisk in both lower limbs. She uses a cane but is able to walk slowly without limp, carefully, holding both arms stiffly at her side as she concentrates on walking. Sensory examination was not detailed due to patient discomfort and long trip from home that was very tiring.

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Treatment: Prednisone was rapidly tapered off. Begin 1 mg low dose naltrexone [LDN]. Begin N-acetyl cysteine [NAC] 600 mg x 3/day for “cold” CRPS – it is reported to take 3 or 4 months to help.

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Reponse: Mom wrote a few days later, “On the way home from our visit in La Jolla, K started to experience sensation in her leg. You had asked her at the appointment if she had numbness and she could feel some in the back of her leg. She didn’t realize the extent of it. The Naltrexone [1 mg] seems to be awakening areas of her leg. She has felt more muscle pain as well. She feels this may be because she is able to use more muscles in her leg with the increased feeling. She also had her foot stepped on the next day (Saturday). In the past, she would have been incapacitated with the pain for a couple weeks. With the Naltrexone, she felt very little pain at all. We were both very excited to see these changes. She is at about a level 3 to 4 in pain.”

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Encouraged mom to continue increasing LDN as tolerated.

11/16/11, ” K is pain free at 3 mg of Naltrexone. We are not sure of any side effects at that level as she has a cold/flu and has had nausea and headaches. She does not have any sleep issues so far. K thought the Delsym was making her lightheaded. She will start it again as soon as she is feeling better.…

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Needless to say, it makes me very happy to know I am able to help someone in pain, especially a child.

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11/21/11: “We are thrilled too! The only things she is taking is the NAC and the naltrexone. When she tried 2mgs the pain receded to just the upper back of the leg. She also noticed the minor cut she had that day burned a lot. At 3mg all pain just vanished. I can’t tell you how excited we are. Her muscles are a bit sore in the leg as she is exerting herself more in physical therapy…. I am interested to see K’s next autoimmune text results in 6 months. I am wondering whether her Autoimmune test results will be negative from taking the naltrexone.”

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1/15/12, “K has been using the LDN at 4 mg and it is working better for her….Once K has recovered from the mononucleosis and is back on her feet again she will know for sure whether her leg pain is gone when standing in one position. If not, she will try the dose at 5 mg and let you know how that goes.”

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Coming soon, though these stand on their own:

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Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness.

This research shows efficacy of analgesics decreasing since 2000.

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“The evidence for pharmacological treatment of neuropathic pain” publication is a good meta-analysis of the current state of evidence-based treatment of neuropathic pain.

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I have quoted extensively from the article as it is important.

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“Abstract: One hundred and seventy-four studies were included, representing a 66% increase in published randomized, placebo-controlled trials in the last 5 years. Painful poly-neuropathy (most often due to diabetes) was examined in 69 studies, postherpetic neuralgia in 23, while peripheral nerve injury, central pain, HIV neuropathy, and trigeminal neuralgia were less often studied. Tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, the anticonvulsants gabapentin and pregabalin, and opioids are the drug classes for which there is the best evidence for a clinical relevant effect. Despite a 66% increase in published trials only a limited improvement of neuropathic pain treatment has been obtained. A large proportion of neuropathic pain patients are left with insufficient pain relief. This fact calls for other treatment options to target chronic neuropathic pain. Large-scale drug trials that aim to identify possible subgroups of patients who are likely to respond to specific drugs are needed to test the hypothesis that a mechanism-based classification may help improve treatment of the individual patients.”

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~The bla

The black circles are recent circles, the light circles are from the past. Shift to the right means less effect.

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“Fig. 1. It shows the combined numbers needed to treat (NNT) values for various drug classes in all central and peripheral neuropathic pain conditions (not including trigeminal neuralgia). The figure illustrates the change from 2005 values in light grey to 2010 values in dark grey.  [emphasis mine]The circle sizes indicate the relative number of patients who received active treatment drugs in trials for which dichotomous data were available. Please note that the differences in study design and the patient populations preclude a direct comparison of NNT values across drug classes (see text). BTX-A: botulinum toxin type A; TCAs: tricyclic antidepressants; SNRIs: serotonin noradrenaline reuptake inhibitors; SSRIs: selective serotonin reuptake inhibitor.”

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“Fig. 2. It shows the combined numbers needed to treat (NNT) values for different drug classes against specific disease etiologies. The symbol sizes indicate the relative number of patients who received active treatment drugs in the trials for which dichotomous data were available.”

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 A disease-based classification: fact or fiction?

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“Since (1) there are no clear indications that specific diseases should be treated with specific treatments, (2) symptoms and signs overlap in various neuropathic pain conditions [6], and (3) currently available drugs act with unspecific neurodepressant actions rather on pivotal pathophysiological mechanisms, at present there is no good rationale for a treatment algorithm that discriminates between underlying etiologies [45]. Nevertheless, the vast majority of trials have been done in painful diabetic neuropathy and PHN and few, if any, in certain other conditions (e.g. Guillain–Barré syndrome and small-fiber neuropathy), and recommending a treatment for other conditions may seem to be an unjustified jump.”

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“Supplementary Figure 1L’Abbé plot showing pain relief for all drugs for different neuropathic pain conditions. Each point illustrates one comparison against placebo (for trials listed in Supplementary Table 1). The axes indicate the percentage of patients with at least 50% pain relief with active and placebo treatment.© 2010 International Association for the Study of Pain”

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Conclusion

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“Pharmacological treatment still represents the main option for treating chronic neuropathic pain. Our understanding of neuropathic pain-generating mechanisms has grown considerably within the last few decades, but unfortunately this research has not been matched by a similar improvement in treatment efficacy. We are still limited in our efforts in managing neuropathic pain by relying on treating the symptoms of pain rather than identifying the underlying disease mechanisms causing the pain. Although 69 new randomized controlled trials have been published in the past 5years compared with 105 published trials published in the preceding 39years, only a marginal improvement in the treatment of the patients with neuropathic pain has been achieved.”

© 2010 International Association for the Study of Pain

The study is part of the European project, funded by the Innovative Medicines Initiative Joint Undertaking

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The material on this site is for informational purposes only,

and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

For My Home Page, click here: 

Welcome to my Weblog on Pain Management!

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Spine Fusions: no better than Cognitive Behavioral Therapy and Exercise

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This report, from the Academy of Neurology may help guide you in decision making: 

Deaths, Complications, Higher Costs Accompany Increase in Complex Spine Fusions Among Elderly.

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“Fusion is usually performed for degenerative disc disease for chronic low back pain, but a number of studies have shown that their outcomes are no better than a combination of graded exercise and cognitive behavioral therapy.”

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Tragically, dementia can result from extensive spine surgery. Many factors can contribute to that. If I were having spine surgery, I would look at the data of dementia following open heart surgery and the protective benefits of ketamine given prior to surgery. Ketamine can spare neuronal function. It is neuroprotective. I link to a publication on that in this post. The problem may be that so few physicians are willing to provide ketamine as they may lack information on its use, yet it is one of the safest medications we have, nontoxic and neuroprotective.

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The material on this site is for informational purposes only,

and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

For My Home Page, click here: 

Welcome to my Weblog on Pain Management!

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Glial research key to intractable pain?

These are not ordinary cases.

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These patients have failed every known treatment for years under the care of well known specialists.

They show a remarkable and lasting response to these simple medications.

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The response is important because these medications are 

(1) available, low dose, nontoxic medications largely ignored by the medical community for pain,

(2) glial modulators, and

 (3) more glial research is urgently needed for millions with intractable pain.

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May 2011: The World Health Organization says undertreated pain is America’s #1 public health problem

Department of Health and Human Services says that patients with chronic pain

outnumber patients with heart disease, diabetes and cancer combined

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Fibromyalgia Disabling, Responds to LDN & Dextromethorphan

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AP, 75 years old with scoliosis, restless legs syndrome, anxiety, seen 8/6/04: Onset of fibromyalgia in 2000 after losing half her investment portfolio. It began with acute onset of severe arthralgias, myalgias, fatigue without fever, that prevented her from returning to her business as an art dealer for corporations, private collections. It disappeared without a trace suddenly in 2 months. She was nearly bedridden, just able to sit in a chair, diagnosed as fibromyalgia by a rheumatologist.

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Two years ago, pain, fatigue and “brain fog” returned in 2002, now disabled with intense muscle ache across upper and lower back, circumferentially in thighs/legs, everywhere except head, trunk, feet, fingers – stable since acute onset, markedly interferes with activity, mood, thinking, walking, sleeping, doing her checking account and driving. Pain ranges 2 to 10, average 4 to 5. Burning pain is recent, across upper thoracic and arms, avoids simple activity to avoid flare.  She rated moderate depression due to pain and inability to be active and live a social life. She has been unable to resume walking, a favorite activity. Exam: very anxious, muscle tenderness 18 points, including buttocks, calves, iliotibial bands, right cervical-thoracic paraspinal more than left. Spine tender at almost every level, maximal at L4-5. Sciatic notches tender. Both legs severely discolored brown from chronic venous insufficiency. Gait very slow, wide based later found due to cerebellar atrophy (MRI).

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Oxycontin was started and changed to fentanyl 50 mcg/hr every 72 hours. Fentanyl was then decreased to 25 mcg/hr after adding Fentora 100 mcg twice daily, Lyrica 50 mg at bedtime, with mirtazepine 15 mg and temazepam 15 mg for sleep. She continued to have marked difficulty walking, concentrating, thinking, and was unable to drive or do her checking account. Constant issues with constipation required multiple preparations for stool softener, laxatives, anti-emetics; hypertension was difficult to control, and she had high anxiety and stress.

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Fibromyalgia was then helped somewhat by pramipexole 0.5 mg twice daily, amitriptyline 20 to 50 mg/day, Lidoderm 5% patches 3 per day, clonidine 0.1 mg twice daily, that allowed fentanyl patch to be discontinued and lowered her opioid requirement down to Fentora 100 mcg bid, still with some constipation but less.

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11/3/08, started low dose naltrexone [LDN] 1 mg – slept only 3 hours that night. On 4 mg, no sleep at all, 1 mg somewhat better, 2 nights after that back to usual sleep but Pain levels low 0 to 3 limited to low back ache.  Before LDN,  pain ranged from 3 to 8, average 5. She had no withdrawal from opioids.  BM’s were excellent for at least 3 days.  Sinemet 25/100 replaced Fentora for restless legs syndrome.

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However, LDN was discontinued a few weeks later as she had so much energy she was hypomanic. Months later she again developed some pain.

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4/8/09 started Delsym 2 teaspoons every 12 hours. Pain dropped to zero. She never needed opioid again, had no withdrawal. A dose of Delsym is the same as long acting dextromethorphan [DM] 60 mg capsules, but 60 mg was too strong for her —- she became hypomanic again. DM allowed her to become pain free. She stopped DM 10 days, feeling so great she forgot to take it until low back pain returned initially mild, then severe. “I started getting back pain, I thought it was just back pain. I have scoliosis, then it became very severe, then realized am I getting fibromyalgia again.”

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After resuming DM, it took only 3 days for pain to come down from 10 to 3-4, then less and less to 1-2 on scale of 10. She was back on DM 4 days. Today, after being off DM and getting return of pain, she is now still using a Lidoderm 5% patch daily to the low back and occasional Aspercreme to groin qhs. Did not need to use these when pain was zero.

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She is 80 years old feeling better than she felt when she was 50!  “My biggest problem is slowing down. I’m 80. I enjoy doing what I’m doing. I like being alive. I’m a little hyper so I stopped drinking coffee.  Hyper because so excited about life, and catching up to what I could have done.” She is now able to clean and organize things she put off for years while in pain. She began designing bathrooms and kitchens for more than one location and waking up after 6 hours of sleep to begin work all day. Her husband describes her as having the energy of ten people. He needs to interrupt her to stop work and have lunch.

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“It changed my outlook, I’m so much happier. I am in heaven. I am back to my mental age of 50. I feel alive with energy, vibrance, lust for life. I drive clearly, I have a brain, my reaction to the wheel, to moving and turning and seeing things is better.”

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10-19-09, with mild recurrence of pain, she was advised to continue DM 60 mg  AM and PM, add naltrexone 4.5 mg PM, continue both for 1 or 2 weeks and discontinue if no more pain.

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7-26-10, experimented with timing and dosage, 4.5 mg LDN best at 5 or 7 AM, 2 to 4 PM, and bedtime.  DM 60 mg twice daily. Voltaren gel qd < 1/2 tsp total in AM only at times variously at hips, back, medial arms, groin, thighs, behind knees where pain occurs when it occurs. Rates pain 0 to 2, avg 0. Has pain if waits too long to take LDN too long.

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“I feel wonderful. I don’t feel high. Normal, comfortable at ease, mentally clear – more than in years, memory is better – even helped dyslexia. Now I’m able to skim reading.” She reads faster, is able to multitask ten things at once and get them all done. Husband says, ”She has boundless energy.” Biggest problem is instability gait, wobbles. Fear of falling. Fell backwards in bedroom one month ago,a  trip and fall onto her back, bruised posterior thoracic and right arm. Had home PT. She works out in gym, treadmill daily. Exam: 2/3 of proximal legs and both feet now normal skin color. Gait slowed. Wide based. MS and mood – excellent. Drowsy [never sits still at home].

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Fall 2010, husband reports her gait markedly improved, faster, more stable after dental prothesis. She is walking faster. She is now 82 and full of energy. Visits initially were monthly for several years while on opioid analgesics, now seen 2 or 3 times a year for minor adjustments and off opioids since 2008.

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Of course all specialists have stories of unusual responses,

but these are responses to the combination of medications that I use, that are not used by other MD’s.

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Transverse Myelitis Responding to Low Dose Naltrexone

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There is currently no known treatment for Transverse Myelitis. It is very rare, if ever possible, to be able to reverse lesions of the brain and spinal cord seen on MRI, especially if chronic. This man is responding to this tiny dose of naltrexone, 1/6th or 1/8th of the smallest tablet.

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FB, 47 year old male triathlete seen 11/1/10. He was in excellent health until 11/09. He began to have interscapular pain worse on the left, days later a band around the waist approximately T8-T10 described as “muscular” discomfort, later with numbness in the same area, followed by weakness, spasticity of the left lower limb and atrophy. Intermittent Lhermitte’s, now resolved. Hypersensitivity to sensation of his shirt across his chest and shoulders lasted 4 to 6 weeks with initial onset. Initially misdiagnosed as Multiple Sclerosis. MRI and spinal fluid led to diagnosis of transverse myelitis.

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On 3/11/10, MRI cervical and thoracic cord [probably the second MRI of two sets of MRI’s] showed extensive parenchymatous lesions extending at least 10 segments from T1-T10 with extra-axial fluid collection that appears as an extensive arachnoid cyst over multiple levels. No obvious cord compression. CSF Mixed lymphocytes with reactive pleocytosis, WBC 2/cu mm, 97% lymphs, 3% monos.

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Diagnoses  11/1/10:  Transverse myelitis with foot drop, spastic monoparesis, atrophy of the left lower extremity, neurogenic bladder, constipation, band around the lower thoracic “waist” onset 11/09, self-treated by injections of B12 with declofenac.   He also had gluten intolerance – eating gluten flares above symptoms

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1/27/11, return visit: “I feel l ike I’ve come light years away” compared to one year ago.

Low dose naltrexone [LDN]  prescribed November 2010, took for few months. Felt immediate effects, improved in strength at left lower extremity, foot drop still present but no longer catches toes on curbs or steps.

He increased dose to 7 or 8 mg, began to feel slightly weird, mild insomnia, like head felt a little weird. Stopped LDN a couple months.

Resumed LDN April 2011,  and again began to feel positive effects; used it daily since then, probably 6 to 7 mg/day.

Resolved: burning pain both feet had radiated up the calves when seen 11/10 ––> discontinued gabapentin one year ago, about 1/10.

Resolved: banding around the waist.

Improved strength 30%  in left lower extremity, still unable to push off with the left foot, but no pain.

Improved: Occasionally used to get a trembling in the left leg evenings 7 or 8 pm, shaking every 20 secs for an hour, at times preventing sleep – resolved about 4 months ago, occurs now perhaps 1 or 2 days a month.

Improved bladder urgency, must find toilet 3 minutes before he voids, now limited to the first 3 hours of the morning.  Before, he could not be far from restroom. Rectal sphincter feels weak.

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In December 2011, he felt symptoms were plateauing, slowly getting better. Went on vacation in January, ran out of LDN for 11 days and is today 30% weaker. That was the longest time he has been off LDN in the last 9 months. The left leg feels a little like spaghetti. When on LDN, he felt stronger when lifting the leg.

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Sleep: When began LDN, had 3 or 4 months of vivid dreaming, but urinated during sleep 2 or 3 times a month while have the vivid dream that he was voiding. That resolved.

Still has weird sensations: right foot a little burning sensation, not pain, of the whole foot, lasting 1 or 2 hours, quite tolerable, nothing like it was before when pain radiated to the calves of both legs.

His medications:  LDN, vitamin D3, alpha lipoic acid, Fish oil 2 or 3/day,

Every couple weeks he gets an injection of B12 and diclofenac 2 vials to buttock and feels definite benefit – I warned not to use diclofenac due to high risk of heart attack, cardiac arrhythmias with this NSAID.

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Spinal Stenosis Pain Responds to Nasal Ketamine

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ML, 81 year old diabetic woman with heart surgery 9 months ago, reports that she was able to walk 26 miles a day in Snow Canyon Utah 10 years ago, but barely able to walk room to room the last year due to lumbar pain and weakness from spinal stenosis. Function failed to benefit from tramadol 100 mg x 3/day and she disliked the side effects. Gabapentin failed to help, but when she tried to stop, she had severe nausea and she lost so much weight in four days that her endocrinologist advised her to resume it.

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Nasal ketamine was started with excellent results allowing her to walk again. Unfortunately, on her own, she abruptly and almost immediately stopped tramadol which resulted in severe opioid withdrawal: severe vomiting, dry heaves and watery diarrhea for 48 hours. She was admitted via ER with chest pressure and muscle strain of abdominal muscles from vomiting. EKG and chemistry ruled out heart attack. Low potassium was corrected and she returned home the next day delighted with pain control.

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A few days after hospital discharge she reports: “Feeling good, actually exercising in the pool every day, 30 minutes without stopping.” Weather here has been sunny 80 degrees this January. “I never built back my stamina after the heart surgery because of the pain.  I think I am finally on the right  track and it feels good!!” Her son is coming over to walk around the block with her tomorrow.

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 Complex Regional Pain Syndrome 70% Better in 6 Weeks after Opioid Detox,

Responding to Low Dose Naltrexone, Ketamine, Lamotrigine, Memantine

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AD, 23 year old male athlete with Complex Regional Pain Syndrome [CRPS] caused him to be bedridden 4.5 years on opioids. Pain was so severe he was unable to eat and lost 30 pounds of muscle. He was slowly able to bear weight and walk 5 or 6 steps with an underarm crutch, but used a wheelchair when not in bed. Fatigue was severe and unbearable just to be out of bed a few minutes. Pain involved all limbs, but focused at the cold right lower extremity, particularly the knee where he had maximal pain. He is tall and weighed 110 pounds when first seen July 2011.

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I advise patients that opioids create pain.  I am guided by a colleague who detoxed thousands of persons in pain over a 20 year period and never once found the patient had more pain after detox. Confirming this, Baron and McDonald published Significant pain reduction in chronic pain patients after detoxification from high-dose opioids in 2006. Some of the science  is discussed here.

~in 2006

This young man decided the night of his first visit to stop opioids and was admitted for symptom control with opioid withdrawal. He was started on low dose naltrexone [LDN], N-acetyl cysteine, dextromethorphan, slow titration of lamotrigine and memantine slow titration, and oral ketamine. Six weeks later he returned and rated himself 70% better, no longer in a wheelchair, not needing a crutch, but still with significant fatigue that caused him to need to lie down during the day. However, he was able to return to his MBA program by September and is doing well in college.

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  CRPS pain 70% Better in 6 weeks on Low Dose Naltrexone [LDN], Patient with ALS

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FG,  a 71 year old woman with Complex Regional Pain Syndrome [CRPS] and severe burning pain in the legs that markedly interfered with sleep, was seen in fall 2011 for pain in the legs that began two years ago after thoracic fusion October 2009, with cage and titanium rods T4-T9. Disc at T5-6 was compressing the spinal cord and there was an asymptomatic T4-T5 compression fracture 4 to 5 years ago. After thoracic fusion she was able to use a walker for a time, but had weakness progressing to paraplegia and had been in a wheelchair for 6 months. ALS was diagnosed at two university medical centers. Her feet were deep purple, swollen twice their size. and now back to normal size after 7 low power laser treatments. She was now having a frequent ache in both deltoids for a few months from needing to use her arms to push up from the wheelchair. Recently she had severe weight loss with shortness of breath, and during sleep used CPAP for obstructive sleep apnea. Polymyalgia rheumatic from year 2000 was in remission – she’d been on prednisone 5 years until 2005. Breathing was shallow, FVC 1.72 is 54% of predicted.

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She had a spinal cord stimulator at T10-11.

Medications tried and failed: Cymbalta 30 mg maximum dose, Neurontin 400 mg BID maximum dose, Lyrica dose unknown. Fentanyl patches no effect.

Methadone 25 mg/day for 1.5 years, is the only medication that helps, estimated 80% relief, nevertheless described pain as severe. She used it 5 of 7 days. With ALS causing progressive respiratory difficulty consistent with neuromuscular disease, it was deemed dangerous to continue an opioid. 

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Low dose naltrexone 4.5 mg to be started after all methadone is out of her system. She was started on N-acetyl cysteine 600 mg capsules x 3/day – the standard of care in Netherlands since 1995 for cold CRPS. Lamictal 25 mg, to begin 1 daily for 2 weeks and slowly titrate to 300 mg per day.

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On return 6 seeks later, she was delighted to report 70% relief of pain. She plans to return if pain progresses.

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Complex Lumbar Disc Disease Markedly Better with Low Dose Naltrexone 

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CL, first seen age 57, December 2004, for pain right buttock radiating to right leg due to degenerative disc disease with lumbar radiculitis. She injured the right knee four weeks prior after giveaway weakness of the right leg. After the recent lumbar laminectomy in June 2003, she had done well only during the months of October, November, December before she herniated the lumbar disc at L3-4 and declined further surgery. The flare occurred after sitting in a chair for 4 hours taking a class. Symptoms were similar to those she had prior to extensive lumbar surgery but she declined repeat surgery. On Exam, she had positive straight leg raising at 45 degrees bilaterally and diminished reflex right knee, but motor, sensory exam was otherwise intact.

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She had received epidurals perhaps 6 per year from 1999 until December 2004, posing a risk for osteoporosis, and she had symptoms of probable ulcer disease from a steroid dose pack. She had extreme pain during the epidural, but got fairly good relief for only one to two months. Pain in the leg now is 50% less from the recent epidural but will it last?

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Past Surgery: Cervical laminectomy and fusion C5-C7 with anterior plate, lumbar hemi-laminotomies L3 to S1 on the right and discectomy right L3-L4 in June 2003. MRI done after surgery 4/30/04: 1.  Large right paracentral recurrent disc herniation filling right lateral recess at L3-4. 2.  Asymmetrical right foraminal & extraforaminal disc protrusion at L4-5.  3. L5-S1, mild right foraminal stenosis due to facet hypertrophy & asymmetrical disc bulging on the right.

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She was started with a Fentanyl patch then changed to Oxycontin but continued difficulty walking, standing, lifting. Flying to Boston to see her son would result in being bedridden for the week in Boston and after returning home. However, a few days prior to another trip to Boston, Namenda 5 mg profoundly helped back pain. She was no longer bedridden but was able to travel up and down the East coast and fly home with markedly improved function. Stretching, doing yoga. Walked briskly on beach with son for quite some time.

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On  8/31/09 , surgery for hyperparathyroidism removed two parathyroid glands on left side, biopsied on right.  Back pain “killing me” on left lumbar side postop, hospital 1-1/2” mattress caused flare. She was not back on Namenda 5 mg as it was too painful to swallow and expensive on her budget.

~

Low dose naltrexone [LDN] was started 12/12/08, after stopping the Fentanyl patch 2 days previously. On January 2009, she reported: “My pain level dropped to about 2-3 at that time and was down to 1 by Dec. 15th. With the patch still in by bloodstream for those few days my pain level never really spiked.  There was a very even transition from the patch to the LDN. What I do know is that my pain level has remained at about a 1-2 for the past month, even with an increased stress level and much time spent on my feet. [She has had lifelong insomnia.] It hasn’t changed my sleep pattern at all.  I still take the Temazepam several times to help me sleep a little bit better. I’m very happy that the LDN has given me so much relief from the pain I’ve dealt with for over 5 years.”

.

1/29/12, she emails, “Although my lower back pain is pretty well controlled, my right knee pain prohibits me from doing many things that I would like to do. However, I had a significant event last night.

.

I awoke at 3AM with terrible stabbing pain going from my right knee to my right foot. I was in too much pain to deal with the Ketamine spray on a Q-tip, so I just used 3 sprays in each nostril, pinched my nostrils together, and tilted my head back slightly. The pain was completely gone in 30 seconds and I was able to go back to sleep immediately. 

.

I used the 50mg/ml dose since I haven’t picked up the stronger spray yet. It was amazing! I’ve continued to use the nasal Ketamine today and it has helped considerably, though not as dramatically as it did at 3AM.

[P.T.] told me there’s nothing more he can do for me.  He said he’d be happy to help me with my re-hab after my knee replacement.  So now I guess I will just have to hope that [my rheumatologist] will be able to offer me some pain relief with hyaluronic acid injections until I can convince myself that a replacement is the only solution.

So the LDN and the Ketamine spray are my constant companions for now.

~~

~

`

 Right Upper Quadrant & Ribs After Laparoscopic Gall Bladder Surgery Better with LDN

~`

CR, 40 year old engineer with scoliosis who had been a triathlete. She first saw me on 6/6/05 for persistent, intense, right upper quadrant abdominal and rib pain that began immediately after laparoscopic gall bladder surgery on 11/17/04, associated with severe fatigue. Pain in the abdominal area was so acute after surgery that she couldn’t swim for four months. Pain impaired breathing and ability to stand erect. She became a long distance swimmer as she now could not do a flip in a pool, run, bike or take part in other sports. Severe pain was triggered even by slight jogging, jarring, vibrations forcing her to buy another car. Positions that relieved right rib pain, made scoliosis worse. Prednisone last year caused loss of memory for  > 1 month of work projects.

~

Spasm along the right lower rib was so severe she once fell out of bed. A cardiologist and neurologist advised removing the lower ribs.

~

Pain was constant mild to moderate at right lower ribs with muscle spasm at the right epigastric area,  intermittently severe stabbing, tender, penetrating, burning.  She describes the pain as a scorpioin tailed dragon that stabs with its scorpion tail and blows fire breath inside the ribs. Pain ranged from 1 to 7, average 4 to 5, and severely interferes with function including ability to concentrate, general activity, enjoyment of life, sleep, work, relations with others and moderately interferes with walking and mood. Each of the 2 times she started P.T., she heard a “pop” when the ribs were released; spreading the ribs relieves pain/spasm.  She tried acupuncture, yoga, Feldenkrais.

 ~

Exam: hyperalgesia over the tender T8 dermatome at the lower right ribs shading off toward T10; easily palpable tender trigger point at right epigastric area that radiates to the right anterior lateral iliac crest suggesting visceral ligamentous problems. Physical therapist noted a stiff band in the right upper quadrant but there are no ligaments in this area of the anatomy. She had temporary relief with adjustments, poor response with opioids and failed gabapentin. Intercostal blocks T8-T10 or T11 and right upper quadrant field blocks using Marcaine gave transient 50% relief. MRI and CT scans failed to disclose any etiology.

By 11/17/05, P.T. had freed several structures about the rib cage, but was not able to loosen the lower ribs that no longer flare out as the left side. P.T. has helped far more than nerve blocks (duration of nerve block effect 2 to 4 weeks if cortisone used, or 5 to 14 days if a field block after miserable numbness 48 hours). Pain is focal at the MCL inferior to the lower right rib, deep under the incisional scar triggered by crunches  (as with use of dishwasher, etc).  She is now able to swim butterfly, but not flip turns – flip turns are a crunch flexion. Right levator scapulae trigger point is flared with the same crunches and “feels related.”  She continues Feldenkrais but avoids flexion,no longer has difficulty breathing and since P.T. has been able to get the inspiration spirometer to the top. Inflammatory pain along the costochondral margins anterior and posterioly from T2 to T12 and below the right lower ribs fairly resolved with the topical ointment ketoprofen 20%, lidocaine 10%. She tried Bengay at the levitator scapulae but stopped Daypro due to burning mid sternum, uses aspirin with yogurt.

~

New spine x-rays were reviewed at Boston Children’s Hospital compared with her most recent 10 year old spine MRI: The ribs are splinted upward where they should be down.  Scoliosis then measured 31 degrees at T1-6, and 28 degrees at T6-11 with the superior iliac crest 1 cm down.

~

February 2009, she started low dose naltrexone [LDN] 1 mg:  For years, pain was 8 to 9, like I had swallowed a fire burning. After LDN it was gone in one hour, zero for 18 hours later returned but much lower 1.5 on scale of 10. Premenstrual pain also was there lower abdominal, prior 3 to 4, down to 1 while taking LDN. A morning swim in ocean usually takes a couple hours of swimming to warm up to get that endorphin high, since LDN now occurs in 20 min. Begins with complete feeling of ease and well being because you’re swimming in cold water, everything is cold and you’re tired, suddenly you’re not tired, its easy, nothing is terrrible anymore, all the frustration melts away. There are no long life threatening events, everything seems easier, you’re happier, and you love everyone. Everyone you see a that moment is beautiful and you love them.  The world is a little slower.  You always feel like you could swim [or run] forever, whereas before that point you feel you can go maybe 5 more minutes.

~
Since mid morning a little hyper – sometimes I am if I have lots of sugar or caffeine [had none], talking faster, less patient slightly -  entire family has ADD or ADHD. 
Slept really well  —- usually has light sleep, poor quality.
I got my desk cleared off for the first time in weeks.
Had sinus headache 1-2 weeks, the head was still unchanged after LDN.
Had night sweats > 10 years, at 4 am none last night, in fact the opposite.  

~

Sleep improves for some while on LDN. It is a morphinan, i.e. morphine like. “I sleep well on LDN… the neuroma in my foot is not gone but hurts less, one of those items I’ve been ignoring because the rib/abdominal pain kept me from hiking enough to care.  So far that’s what I’ve got, for some reason the best dosing for me seems to be alternating 2mg and 3mg. I don’t know why that is. I still get a good endorphin rush pretty early into exercise, even walking which I can do again.  Last week I accidentally walked 6 miles, longest I’ve walked in years!  Next I want to try hiking once the snow is gone.

~

A stingray stabbed her the top of her foot on 4-28-11. Lifeguards usually call EMT for morphine as the injury causes so much pain that people black out. There was profuse bleeding, estimated one cup of blood, and swelling the size of an egg. The entire foot was covered with blood as were the footsteps on the beach. Pain quickly increased to 7 on scale of 10 but never went above ankle, then pain dropped to a 3 before they were able to put her foot into hot water. She was laughing with the lifeguard while being treated.  Swelling was almost gone 4 days later. It was a little tender to pressure, the puncture was still visible. She did not wear a shoe to avoid pressure over the wound, and to keep the wound clean to avoid bacterial infection. People were asking why she was not walking with crutches – not remotely necessary.

~

She has scoliosis and wore braces for it as a child. “I’ve been using the SalonPas patches on my lower back, they give me a minor skin rash but work great. I suspect a combination of topicals and stretches will be the key.  For meds we’d have to be in the office with my records (allergic to tylenol and bad reactions to naproxen/Aleve though I may try it again some day).  Its more a question of what to do about the underlying cause -the spine- and avoiding the pain. I know having the pain isn’t good long term but its minor enough that I really didn’t feel it all this time because my front hurt more.  Peeling the onion!  While I was having a lot of rib pain I would get pulled forward and my lower back would go “out.” P.T. could help that by loosening the front and working the back.  Now it seems more complex to address.  I used to do lots of sit-ups and crunches to stabilize it but P.T. says no to those and my core is pretty stable.  I have been able to do yoga again (another LDN success) and I thought that helped in the past.  I’ll have to continue with that and see if it helps things in the long run….  I have to seek out the spine experts now that I can move more.  My ski turns are uneven, always have been becuase I turn easier to the left than the right (so I’ll turn one cheek more readily than the other).”

>

Vibrations from dolphins ease the pain for days. She has experienced more encounters with dolphins and whales since the surgery. One day when she was aware of squid in the water, she noticed what she thought was the world’s biggest squid swimming 10 feet below her, except that it was a gray whale, which soon surfaced and blew water. Her reasoning for why marine life are attracted to her: scar tissue built up around her surgical scar, which she says makes a squeaking sound in the water. “It might be similar to how they perceive pain and illness.They might be coming together to try to help.”

.

~

~~~~~

Further information will be posted on these cases, and more cases will be added as time permits.

They will include persons who had years of intractable chronic pain that severely limited function, who are now pain free

on low dose naltrexone [LDN] and/or other medications.  Some with intractable chronic pain have now been pain free off LDN and all pain medications for three years.

~~~~~

The material on this site is for informational purposes only,

and is not a substitute for medical advice,

diagnosis or treatment provided by a qualified health care provider.

~

~

For My Home Page, click here: 

Welcome to my Weblog on Pain Management!

~~

Method for tapering off the last 2 mg tablet of Subutex

~

This step is very difficult.

`

It has been a puzzle for physicians.

~

Subutex is much stronger than most doctors understand. The FDA does not publish how strong it is compared to morphine because it is approved in the US only for opioid addiction, and potency is important only for pain control. But many pain specialists find subutex may control  pain far better than other opioid analgesics without the same side effects. Europe has approved Subutex for both pain and addiction.

~

One milligram of Subutex is equal to 30 to 50 mg of morphine which means 2 mg Subutex equals 100 mg morphine. If it is important to take someone off all opioids, it is best to slowly taper off. Before proceeding to the use of Butrans patches, check the EKG. Prolongation of the QTc interval is listed as a warning for the patch, but curiously not for the much stronger tablet or film of the same buprenorphine.

~

How to Taper

~

1. Begin 3 Butrans patches and stop the daily 2 mg Subutex tablet (or 2 mg Subutex film).

Each Butrans patch delivers 0.5 milligram of buprenorphine, thus 3 Butrans patches = 1.5 mg/day. The patches last one week.

~

2. Decide if you wish to reduce the dose every week or perhaps drop the dose every second or third week or six weeks, whatever you choose.

~

3. When you drop the dose again, then apply only two Butrans patches every week before next change.

~

4. Then one Butrans patch every week.

~

Then stop all Butrans when ready.

~

If the patient is using Butrans for control of substance abuse, that decision will need to be between their addictionologist and their psychologist or psychiatrist. Emotional stability and understanding of triggers for addiction must come first before making the important decision or relapse may occur.

Poorly managed pain can evolve into chronic disease of the nervous system

~

Ketamine is an important analgesic, more important than opioids. It can dramatically reduce pain, and rapidly relieve depression and PTSD.  Please read my earlier posts here and here. And the NPR report here just after I posted this (skip to their last section). Yes, it is FDA approved and legal. One woman said:

.

 ’It was almost immediate, the sense of calmness and relaxation.

‘No more fogginess. No more heaviness. I feel like I’m a clean slate right now. I want to go home and see friends or, you know, go to the grocery store and cook the family dinner.’

.

NPR again reports ketamine’s rapid relief of depression. A 28 year old man whose refractory depression began at age 15, after ketamine, says:

.

‘I Wanted To Live Life’

.

Stephens himself has vivid memories of the day he got ketamine. It was a Monday morning and he woke up feeling really bad, he says. His mood was still dark when doctors put in an IV and delivered the drug.”Monday afternoon I felt like a completely different person,” he says. “I woke up Tuesday morning and I said, ‘Wow, there’s stuff I want to do today.’ And I woke up Wednesday morning and Thursday morning and I actually wanted to do things. I wanted to live life.”.

.

Since then, they treated him with Riluzole that is FDA approved for ALS and has one of the dirtiest side effect profiles I have ever seen in medicine with serious organ toxicity. Ketamine rarely causes mild transient side effects, usually none. It appears the concern is how ketamine is used on the street with potential for abuse. I do not see ketamine abuse in my patients, some of whom are on opioids for pain or Valium family medicines from their psychiatrist. All of those have a greater potential for abuse, also not occurring in my patients. Pain and/or depression can lead to suicide.

.

About 18 months ago, researchers at Yale found a possible explanation for ketamine’s effectiveness. It seems to affect the glutamate system in a way that causes brain cells to form new connections.

.

Researchers have long suspected that stress and depression weaken some connections among brain cells. Ketamine appears to reverse the process.

.

It would be of interest to see a case report of the bladder problems they mention. Is this in a single drug addict who used many unknown medications on the street? Several physicians have infused IV ketamine for persons with pain for many years, in far higher doses than I prescribe, with no report of any but transient minor symptoms.

.

David Barsook’s 2009 review, reference below, describes changes that cause memory loss and brain atrophy with chronic pain, in particular, Complex Regional Pain Syndrome (CRPS), and they also occur with chronic depression:

~

With the onset of chronic pain (including CRPS) a number of changes in brain function occur in the human brain including but not limited to: (1) central sensitization ; (2) functional plasticity in chronic pain and in CRPS; (3) gray matter volume loss in CRPS ; (4) chemical alterations; and (5) altered modulatory controls. Such changes are thought to be in part a result of excitatory amino acid release in chronic pain. Excitatory amino acids are present throughout the brain and are normally involved in neural transmission but may contribute to altered function with excessive release producing increased influx of calcium and potentially neural death.

.

Brain atrophy and memory loss has also been shown in chronic low back pain as well as in chronic depression.

~

Barriers to management of chronic pain are many:

~

Although opioids are effective for acute pain, effective treatment of chronic pain is often daunting, particularly neuropathic pain.

~

Opioids have been shown to create pain causing imbalance in the glial cytokines that favor pain rather than relief of pain. Opioids carry the risk of opioid-induced hyperalgesia which is a severe pain sensitivity. They affect the brain and endocrine system. Opioids may fail to offer significant relief, fail to improve function, and risk misuse, abuse, diversion and death. Their costs are astronomic, insurance coverage is increasingly limited, the potential for complications may be life threatening in a hectic medical setting, side effects can be lethal, lack of physician training in use of opioids and alternatives to pain control lead to increasing deaths, addiction and diversion. It has become a national emergency and a trillion dollar war on drugs.

~

Complications can be greatly reduced through use of a scrupulous history and physical examination, but reimbursement is directly proportional to the shortest time spent with a patient. Will that help assessment and care?

~

Individuals may have dramatically different responses to opioid therapy; some may not tolerate any, and relief must be balanced with side effects that increase as the dose increases. Patient status may change and require IV, rectal or tube delivery instead of oral formulas; drug-drug interactions may require rapid changes, and disease of kidney, liver or brain may require modifications or stopping altogether. They may increase risk of falls and cause central sleep apnea with drop in oxygen because the brain fails to give a signal to breathe.

~

Chronic pain can lead to loss of sleep, hopelessness, depression, anger and other mood disorders such as panic, anxiety, hypochondriasis and post traumatic stress disorder [PTSD]. Treatment of mood disorders are shown to profoundly reduce pain perception and/or ability to cope with pain.

~

Ketamine is anti-inflammatory and can reduce the need for opioid use, thus reducing the pain and side effects caused by opioids.

~

Nasal ketamine is more effective than oral ketamine for pain relief; oral dosing has no effect on depression.

~

Nasal delivery of ketamine is now possible due to advances in metered nasal sprayers that deliver a precise dose. No needle is required, no IV access, no travel to a specialist needed.

~

You can carry pain relief with you and use it as directed when it is needed.

~

Ketamine is an NMDA antagonist: it antagonizes the NMDA receptor which plays a profound role in pain systems and centralization of pain.

~

Ketamine is neuroprotective and it can help other disease states  as noted by Barsook, 2009:

~

Besides improvement in pain, “there may be lessons from other diseases that affect the brain; it is noteworthy that acute ketamine doses seem to reverse depression and ketamine decreased prevalence of post-traumatic stress disorder (PTSD) in soldiers receiving ketamine during their surgery for treatment of their burns. In addition ketamine attenuates post-operative cognitive dysfunction following cardiac surgery that has been known to produce significant changes in cognition. [emphasis mine] The data suggest that the drug can alter or prevent other conditions based on its NMDAR activity where other drugs NMDA receptor antagonists are perhaps not as effective in these or pain conditions. Lastly, NMDA antagonists have been used in degenerative disease (and pain may be considered a degenerative disease as defined by loss of gray matter volume, see above) with mixed effects perhaps relating to how they act on specific NMDA subtypes. Taken together, ketamine may act not only on sensory systems affecting pain intensity, but also on a constellation of brain regions that are involved in the pain phentype. [sic, phenotype]“

~

Side Effects

~

Ketamine is more frequently used in babies and children than in adults because high doses of ketamine can induce hallucinations in the adult. Importantly, it is used in high dose in adults for treatment of Complex Regional Pain Syndrome.

Low doses, cause little or no side effects in adults. If present, they are transient and often resolve in 20 minutes. Patient who respond to ketamine report good acceptance as they find the relief of pain and/or depression far outweighs any short term minimal discomfort.

~

Pain care reform is urgently needed.

~

Research funding for pain is less than half of one percent of the NIH budget. More research is needed, but research on low dose ketamine for treatment of pain and depression has gone on for twenty years.

The public health crisis of untreated pain, which often results in disability, parallels the country’s struggle to halt the cost of health care. The longer a person remains with untreated pain, the less likely they are to return to work or to be employable.

~

Conclusion

~

Pain control requires urgent attention. It is past time to put into practice the use of this valuable medication so people can get on with life instead of being mired in chronic pain that for many risks suicide and ensures continuing decades of disability. Academic studies are usually limited by defining a predetermined dose rather than clinically titrating to effect. Thus no surprise, they find no effect as every patient will have no response until they reach their dose. And that dose, in my experience, falls into a bell shaped curve. One size does not fit all. Some respond at very low dose, others require much more, and the majority fall between.

~

In my experience prescribing ketamine for ten years, only a rare person has problems. Almost all find it has returned function or significantly relieved pain. Some have been able to entirely eliminate opioids that did nothing for their pain for decades, though they dutifully returned to the MD every month to chronicle that pain. Pain continued to be rated ten on a scale of ten; patient always compliant despite side effects of constipation and often depression. My patients find the benefits of nasal ketamine far outweigh the relief of oral ketamine and at much lower doses with fewer side effects.

~

Further, while the pain relief may be short lived, some find it gets better with repeat dosing, and relief of depression may last one to two weeks with a single dose.

~

References

~

http://www.wjgnet.com/1007-9327/10/1028.asp  Ketamine suppresses intestinal NF-kappa B activation and proinflammatory cytokine in endotoxic rats.

~

CONCLUSION: Ketamine can suppress endotoxin-induced production of proinflammatory cytokines such as TNF-a and IL-6 production in the intestine. This suppressive effect may act through inhibiting NF-kappa B.

~~

Crossover, 20 patients. Ketamine reduced breakthrough pain within 10min of dosing, lasting up to 60min

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2875542/  Ketamine and chronic pain – Going the distance, David Barsook, 2009

• PTSD has a more direct link to suicide than previously thought, a current Texas A&M University study concludes – references below.

• A high lifetime risk of suicide occurs in women who have been sexually and physically abused as young girls.

• More than 300,000 veterans have been diagnosed with PTSD or major depression – many not yet diagnosed.

• Risk of suicide is the highest during the first month of standard antidepressant therapy, and a significant number of patients do not have adequate improvement even after months, resulting in harm to personal and professional lives.
  

• Patients are at suicide risk upon discharge from psychiatric hospitals.
  

• Significant predictors of both suicide attempts and preoccupation with suicide are guilt and anger and impulsive behaviors.

  ~
  ~

• Ketamine is the most important breakthrough in treatment of major depression with rapid and lasting effects.

• Ketmine helps immediately, unlike all other antidepressants that may require weeks or months to work, if they help at all. See NPR report here - that appeared soon after I posted this (skip to their last section). It is FDA approved and legal. NPR again reports ketamine’s rapid relief of depression. A 28 year old man whose refractory depression began at age 15, after ketamine, says:

  .

  ‘I Wanted To Live Life’

  .

  Stephens himself has vivid memories of the day he got ketamine. It was a Monday morning and he woke up feeling really bad, he says. His mood was still dark when doctors put in an IV and delivered the drug.”Monday afternoon I felt like a completely different person,” he says. “I woke up Tuesday morning and I said, ‘Wow, there’s stuff I want to do today.’ And I woke up Wednesday morning and Thursday morning and I actually wanted to do things. I wanted to live life.”.

  .

  Since then, they treated him with Riluzole that is FDA approved for ALS and has one of the dirtiest side effect profiles I have ever seen in medicine with serious organ toxicity. Ketamine rarely causes mild transient side effects, usually none. It appears the concern is how ketamine is used on the street with potential for abuse. I do not see ketamine abuse in my patients, some of whom are on opioids for pain or Valium family medicines from their psychiatrist. All of those have a greater potential for abuse, also not occurring in my patients. Pain and/or depression can lead to suicide.

  .

  About 18 months ago, researchers at Yale found a possible explanation for ketamine’s effectiveness. It seems to affect the glutamate system in a way that causes brain cells to form new connections.

  .

  Researchers have long suspected that stress and depression weaken some connections among brain cells. Ketamine appears to reverse the process.

  .

  It would be of interest to see a case report of the bladder problems they mention. Is this in a single drug addict who used many unknown medications on the street? Several physicians have infused IV ketamine for persons with pain for many years, in far higher doses than I prescribe, with no report of any but transient minor symptoms.

  .

  Memory loss and brain atrophy occur with chronic depression, reported by the National Institute of Mental Health ~2001. The mechanism is described by Barsook referenced here.

  ~

• You do not need to be hospitalized.
  

• A single low dose ketamine treatment, given nasally, can reduce core symptoms of PTSD and depression. It can save your life.
  

• Relief of depression can occur in 2 minutes to 2 hours and may last 1 to 2 weeks.
  

• National Institute of Mental Health published 100% relief in a group with depression refractory to all treatment that failed as long as 43 years.

• You cannot anticipate when suicidal thoughts occur, but you can carry ketamine with you for instant relief.
  

• There is no other medication besides ketamine that gives 100% relief. Not one.
  

• Ketamine is not toxic, not expensive, side effects if any are transient – usually none. It is compounded by pharmacy.

  ~

• I can help. I’ve prescribed this medication for 10 years, spoken with some of the world’s foremost psychiatrists. Some of my patients with profound pain/depression travel to Germany for high dose ketamine coma treatment of RSD/CRPS and tolerate those doses. Ketamine is safe even in babies and children. Very few MD’s prescribe ketamine, and even fewer have much experience with it.
  

  ~

• I need to examine you in person.
  

• I can meet you at my office and it is essential that you meet with my colleagues, a psychologist and psychiatrist.
  

• Times is of the essence because we may need to adjust the concentration of ketamine. We need to determine your comfort level with its use.
  

• This must be a team approach due to your risk and mine.

• If you live long distance, this team should include your local psychiatrist, or one nearby, who will prescribe ketamine for depression. We can help you find a specialist.
  

• Alternately, I will need to see you in my office every few months to renew the medication.

  ~

• The medical literature on ketamine use is profoundly important. There are over 6,800 medical publications. 

• Ketamine has potent healing powers. Karl Jansen, psychiatrist in London, believes that “ketamine has potent healing powers when used as an adjunct to psychotherapy.” There is nothing like it; however, treatment for serious depression still requires team support, not medication only.

  ~

• Suicide is a catastrophic medical emergency. I cannot stress this enough. Depression is treatable.
  

• Your death is unnecessary. It would be a terrible loss to all who love you.

  ~
  ~
  ~

  
  References
  ~

  
  http://emedicine.medscape.com/article/2013085-clinical#aw2aab6b3b3 Suicide Clinical Presentation
  

http://www.ptsd.va.gov/professional/pages/ptsd-suicide.asp The Relationship Between PTSD and Suicide  

PTSD alone out of six anxiety diagnoses was significantly associated with suicidal ideation or attempts. Anger and impulsivity have also been shown to predict suicide risk in those with PTSD.

______

Articles, below, support use of ketamine for rapid relief of depression, even for resistant bipolar depression. The lead author of the first three studies is Carlos Zarate, M.D., Chief of the Mood and Anxiety Disorders Research Unit of the National Institute of Mental Health, NIMH:

http://www.ncbi.nlm.nih.gov/pubmed/20673547   Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder

100% response in persons with refractory depression: 29% went into remission, another 71% were responders.

http://archpsyc.ama-assn.org/cgi/content/full/67/8/793  A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression It even works for resistant bipolar depression

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726824/figure/F1/  Ketamine and the next generation of antidepressants with a rapid onset of action

Potential targets for ketamine and similar agents induce rapid and sustained antidepressant effects. A diagram scientists and physicians will find useful for mechanisms. “Notably, ketamine’s rapid antidepressant effects have been shown to be modulated by AMPA relative to NMDA throughput. Excessive glutamate also stimulates the extrasynaptic NMDA receptors, which antagonizes the activation of neurotrophic cascades. The potential sustained (sub-acute) antidepressant effects of ketamine are hypothesized to be mediated by increases in CREB and BDNF expression, as well as the anti-apoptotic protein Bcl-2.”

https://www.sciencemag.org/content/329/5994/959.abstract mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists

“The rapid antidepressant response after ketamine administration in treatment-resistant depressed patients suggests a possible new approach for treating mood disorders compared to the weeks or months required for standard medications….Our results demonstrate that these effects of ketamine are opposite to the synaptic deficits that result from exposure to stress and could contribute to the fast antidepressant actions of ketamine.”

http://psychiatry.jwatch.org/cgi/content/full/2010/1008/5 Ketamine’s quick antidepressant actions

“The resulting protein synthesis and neuronal alterations in the medial prefrontal cortex are the opposite of those produced by chronic stress….”

 

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~

~

The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

~

~

~

The Immune System and Pain

`

There is a whole new way of thinking of about pain that has nothing to do with pain being

transmitted by nerve cells in well defined nerve pathways.

`

In the last few years, we have learned it has to do with activation of glia and the immune system.

`

Pain is a central neuroimmune activation.

There is close interaction of nerve pathways and the central immune system.

`

Neuroimmune responses parallel but do not always mirror peripheral immune responses.

The differences are critical.

`

The science of understanding immune cell-glia and glia-neuronal interactions is in its infancy.

`

What are glia?

`

Glia are cells in the central nervous system (CNS), the brain and spinal cord. Ninety percent of the cells in the CNS are glia – microglia, astrocytes, oligodendroglia, perivascular glia. Glia outnumber neurons by a factor of 10 to 1.

.

Microglia and astrocytes are immune cells that can release inflammatory responses with harmful effects on nerve cells such as inflammation, toxicity, and excitability. However, scientists are beginning to show that activation may also lead to good outcomes that are helpful for nearby glia and neurons, protecting against inflammation, toxicity and restoring normal pain signaling. In other words, they can restore balance.

`

Beneficial and pathological microglia

.

Neuroinflammation is a normal and necessary process in the acute phase, but not when it takes on a life of its own and creates persistent pain or disease directed against normal tissue (autoimmune response). They may fail to release protective agents (e.g. BDNF, Brain-Derived Neurotrophic Factor).

“

.

Neuron-glia Tetrapartite Synapse

Glial activation from pro-inflammatory to anti-inflammatory state

(click image to enlarge)

Image from Milligan, E, Watkins, L. Pathological and Protective Roles of Glia in Chronic Pain,

Nature Reviews 10:23-36 (2009)

..

Neuroinflammatory Disorders

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There is an growing body of evidence that shows many diverse diseases are characterized by neuroinflammation, such as Alzheimers, Parkinson’s Disease, ALS, Multiple Sclerosis, neuromuscular and myofascial syndromes and neuropathic pain, fibromyalgia, and chronic fatigue syndrome. Our research plans to show activation of glia in other conditions: Tourette’s Syndrome, dystonia, blepharospasm, and torticollis. A neuronal model no longer works to explain these conditions.

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What the heck is microglial activation and priming?

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How do glia become activated? They are always active, not activated but active, surveying their environment. Something must occur for them to become activated. Similar to a bee sting that primes your immune system, the first bee sting will not kill the person who is allergic, but BOOM! the second sting can kill. Glia can become primed by a first pain, but when pain next occurs, glia become activated and they respond faster, harder, longer.

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When activated, they change shape like amoeba and migrate to the site of injury or infection or stroke or dead cells where they proliferate, release cytokines, and phagocytose (consume) targets such as virus, dead tissue, important in wound healing. Microglia and astrocytes can release neuroexcitatory and pro-inflammatory products and growth factors for pain and hyperalgesia. See links to several recent publications on glia here, and mechanisms here and here. Microglia can repair the CNS. Or, an injury may heal and be long gone, but chronic pain may persist for years. How do we turn it off? The signal is no longer telling us about a new danger.

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The goal of research is to find ways to interact with the cascades of pro-inflammatory molecules and receptors to restore balance in the system. This is a major paradigm shift in treatment of chronic pain that has already led to many insights. Refer articles here.

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Toll Like Receptors

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Like all immune competent cells, glia have a myriad of receptors on their cell surface membranes. One of the more important are the Toll Like Receptors (TLRs) that are innate immune receptors in the CNS, discussed here. See image, below. TLRs “are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated….These studies have shown that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis and asthma…. [They] may contribute to susceptibility to severe neonatal inflammatory diseases, allergies, and autoimmune diseases.” Other studies have shown “Toll-like receptors (TLRs) are essential in the host defense against infections. They also have functional roles in tumor progression and their ligands affect tumor cell proliferation, anti-apoptosis and immune escape. The expression or up-regulation of TLRs has been detected in various tumor cells.” “Dysregulation of these signaling pathways has severe consequences, and causes many autoimmune diseases and chronic pathological inflammation.”

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The Toll Like Receptors are not like other receptors. Not these snug little pockets where naltrexone binds. Instead the Toll Like Receptors are like an entire football field, with enormous nooks and crannies. Unlike other receptors, they have enormous interactions with many molecules and medications, e.g. naltrexone is a TLR4 inhibitor, an immune modulator, amitriptyline is a TLR4 inhibitor. And “Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression.” That source is referenced here. Opioids create pain, not just the dread opioid induced hyperalgesia. Glia also contain cannabinoid receptors. Glia produce endogenous cannabinoids and they inactivate them.

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Toll-Like Receptors.

(Image courtesy of SABiosciences, click to enlarge)

Their action on IL-10 is key and more on that will be posted here later.

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Antibodies for pain?

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Some pain syndromes have been found to produce distinct antibodies.

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There is small but growing evidence that the immune system plays a role in Complex Regional Pain Syndrome, CRPS. These individuals have inflammatory markers in spinal fluid and tissue fluids. Recent studies have found antibodies against nervous system structures, specifically, “autoantibodies against an inducible autonomic nervous system autoantigen” in 30 to 40% of persons with CRPS.

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In 2010, a small study found that intravenous immunoglobulin (IVIG) can provide relief in a tiny percentage of patients. IVIG potentially interferes with those autoantibodies and reduces, i.e. downregulates, the inflammatory cytokines that are important in mechanisms of pain and hyperalgesia in the brain and the body. This study has many limitations but it is a first for IVIG.

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JJ Van Hilten et al have found HLA antigens associated with Complex Regional Pain Syndrome with fixed dystonia. “Our results encourage future studies to evaluate the role of HLA-B62 and HLA-DQ8 in different subtypes of CRPS.” This gene family has important immunologic functions.

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And, epidemiology studies show that persons with CRPS are more likely to have asthma.

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The study of glia is in its infancy but it is growing rapidly in many directions. There are drugs that can distinguish activated glia for targeted treatment, new methods of visualizing glia, new sites for pharmacologic intervention, and nanotechnology to deliver medication directly to the inflammation. ` More will come provided there is philanthropic support for this work. It is heartbreaking that NIH contributes less than 1% of its research dollar to pain.

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My thanks to the Reflex Sympathetic Dystrophy Syndrome Association, RSDSA.org, for sponsoring a workshop on Glia and Neuroinflammation that brought together the world’s foremost scientists and provided a unique forum for them to interact and learn from each other.

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It is hoped that their next workshop this year will be on imaging glia. We need to extend the work that has barely begun.`

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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This is a database of persons who have tried low dose naltrexone, their diagnosis, dosage and response to it, if any. The database lists many different medical conditions.

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For example, persons with Multiple Sclerosis, will choose the link above, that has hundreds of persons with MS who have tried naltrexone. Don’t forget to see more pages once you reach the bottom. For a graph of the overall responses, then go back to the main link on Multiple Sclerosis where you see these choices:

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To view the database please click HERE

To view the Graph on how people feel about LDN please click HERE

To add your experience with LDN please click HERE – of course first select the condition you have, so your entry falls into the proper category.

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If your condition is different, just select the condition from the list on left.

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For example for fibromyalgia:

To view the database please click HERE

To view the Graph on how people feel about LDN please click HERE

To add your experience with LDN please click HERE

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Here for Irritable Bowel Syndrome, Crohn’s or Ulcerative Colitis.

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If your condition is not listed, check Other on the left side of the list.

This forum is from LDN Research Trust, a registered non-profit Charity based in the UK, with participants from many countries internationally.

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I will soon be posting several case reports of my patient responders, persons with intractable pain from various conditions. Some have been pain free one or two years on naltrexone. Some who had years of previously intractable pain have responded to low dose naltrexone and remained pain free more than one year after discontinuing LDN.

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MECHANISM

for those who like to know the science

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We have known for decades that naltrexone binds to the mu opioid receptor. It blocks the effect of opioids like morphine at the mu receptor. We now know it also acts at another receptor.

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You may wish to watch this video that explains Toll Like Receptors, TLRs for short. This is a lecture by Dr. Rachel Allen, whose PhD in immunology is from Oxford University. After that, she worked at Cambridge University on innate immune receptors such as the TLR’s.

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In 2008, it was shown that naltrexone binds at one of the Toll Like Receptors, the TLR4 receptor. There are 13 Toll Like Receptors, and so far they have studied naltrexone only at one of them, the TLR4. That is important because the TLR receptors are part of the innate immune system.

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The Toll Like Receptors are not like other receptors. Not these snug little pockets where naltrexone binds. Instead the Toll Like Receptors are like an entire football field, with enormous nooks and crannies where it has many interactions with many molecules. Now, in 2010, scientists are asking if naloxone or naltrexone is acting at TLR4 or even higher up in the cascade.

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The study of immune cell glial interactions is in its infancy. Glial cells are the immune cells in your central nervous system (brain, spinal cord). They are very involved in dysregulation of pain systems, neuroinflammation, and some neurological diseases such as Multiple Sclerosis, Alzheimer’s, Parkinson’s Disease, ALS, infections of the brain, etc.

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One of our distinguished glial scientists, Linda Watkins, PhD, in October 2010, said we are not even sure naltrexone binds to the Toll Like Receptor. Rather, it involves AKT1, close to the TLR4 receptor, very very high up in the cascade at the dimerization step, the recruitment of CD14. This is being worked out now.

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Dr. Watkins with Kennar Rice, PhD, from NIH/NIDA, et al, has a paper in press in Cell:

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Glial activation participates in the mediation of pain including neuropathic pain, due to release of neuroexcitatory, proinflammatory products. Glial activation is now known to occur in response to opioids as well. Opioid-induced glial activation opposes opioid analgesia and enhances opioid tolerance, dependence, reward and respiratory depression. Such effects can occur, not via classical opioid receptors, but rather via non-stereoselective activation of toll-like receptor 4 (TLR4), a recently recognized key glial receptor participating in neuropathic pain as well. This discovery identifies a means for separating the beneficial actions of opioids (opioid receptor mediated) from the unwanted side-effects (TLR4/glial mediated) by pharmacologically targeting TLR4. Such a drug should be a stand-alone therapeutic for treating neuropathic pain as well. Excitingly, with newly-established clinical trials of two glial modulators for treating neuropathic pain and improving the utility of opioids, translation from rats-to-humans now begins with the promise of improved clinical pain control.

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For chronic pain, targets of interest are: glial attenuation, p38 MAPK inhibition.

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Of interest, a commonly prescribed pain medication, amitriptyline, is a TLR4 inhibitor (Hutchinson, 2010).

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You can read many new publications on glia that I posted on my site here, or find it from the banner at top:

Donate to Eliminate Neuropathic Pain

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I am a member of a Neuroinflammation Research Consortium that will be studying these many conditions, some that are painful, others that are not. They involve glia and neuroinflammation.

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For more discussion of mechanisms of action of naltrexone and other publications I have posted, see here, particularly the paper by Zhang, Hong, Kim et al.

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Finally, for those who may feel they are losing heart because medicine has been too slow to adopt the use of low dose naltrexone, let me point this out:

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Dr. Linda Watkins is a University of Colorado Distinguished Professor of Psychology & Neuroscience at the University of Colorado Boulder. She is a world-renown leader in glia research and the neurological applications of glial attenuation, with a focus on alleviation of chronic pain. She is the recipient of the highest award for distinguished basic science research from the American Pain Society and the 2010 John Liebeskind Pain Management Research Award from the American Academy of Pain Management. She has over 300 peer-reviewed publications including articles in Nature, Science, Nature Neuroscience, and Journal of Neuroscience. She received over $2 million in NIH grants supporting 6 generations of IL-10 gene therapy research culminating in XT-101.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

I see long distance patients in my office who generally come for a two week stay, and I wish to encourage their comments on this page. I am sorry I did not post this page for them sooner.

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Most people I see have been tried on every common approach to treatment for Complex Regional Pain Syndrome, CRPS. I prescribe most of those therapies as well, but I also use an expanded number of neuropharmacology approaches. Some of these are outlined in the case report I filed in March 2010.

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In my opinion, it is important to use rational polypharmacy. When pain is intense, it is important to look at more than one mechanism. Once pain comes under control and remains at zero, then we can slowly begin to taper off one at a time.

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The following describe two of the several mechanisms of interest to me.

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NMDA Antagonists

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The glutamate-NMDA receptor is profoundly important in controlling pain pathways. It is responsible for tolerance to medication and centralization of pain. Research in France has shown that with chronic pain in persons with CRPS there is an increase in NMDA receptors in the central nervous system. After pain control, the increased number of NMDA receptors returns to normal.

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With persistent pain or chronic depression, glutamate increases and becomes excitotoxic. When it attaches to the NMDA receptor, it causes calcium to enter the neuron, creates free radicals, and kills neurons. This leads to brain atrophy and potentially memory loss.

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The goal is to block this mechanism. I use three medications that work at this level.

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Morphinans – Glial dysregulation of pain pathways

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Another important area of focus for me are the morphinans which means morphine-like. Their mechanism of action is at the microglia, the immune cells in the central nervous system. There is important new research on glial dysregulation of pain pathways. Once primed and activated by pain, the next pain insult causes glia to react harder, faster and longer perpetuating pain with cascades of pro-inflammatory molecules. Glial research on pain is very recent, very new, very important, and is a rapidly growing  body of science. It offers an entirely new paradigm for treatment of chronic pain.

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The Reflex Sympathetic Dystrophy Syndrome Association library has

many research articles that you may wish to read.

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I am grateful to be invited to their workshop on activated glia.

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Oth

Contributing Factors

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I look at the whole person, review all of their medications including their vitamins and botanicals, toxicity and adverse interactions with medication. I check the blood level for 25(OH) vitamin D (done at ARUP labs), parathyroid hormone (PTH) if not already done, and stress the importance of anti-inflammatory diet, fish oil, and adequate levels of vitamin D3.

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Spinal cord stimulators – controversy

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A recent Wall Street Journal article discusses some of the controversy of interventional techniques in this evolving specialty and mentions that some studies are underway to show efficacy. Implantable devices are controversial “and questions remain about the appropriateness of their use.”

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In April 2010, new guidelines were published, updating earlier ones from 1997: Practice Guidelines for Chronic Pain Management: An Updated Report by the American Society of Anesthesiologists Task Force on Chronic Pain Management and the American Society of Regional Anesthesia and Pain Medicine.

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“Spinal cord stimulation: One randomized controlled trial reports effective pain relief for CRPS patients at follow-up assessment periods of 6 months to 2 yr when spinal cord stimulation in combination with physical therapy is compared with physical therapy alone (Category A3 evidence).”

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A3 evidence was defined as: “The literature contains a single randomized controlled trial.”

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The guidelines had no references, nor did it indicate how old that study was. A short two year followup and a single limited study after more than 32 years of implanting these devices should call for more research.

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I do not recommend spinal cord stimulators as there is no research showing long term efficacy and no quality evidence showing they are superior treatment. Success declines after placement and that may occur the first day. In fact, there is one long term 5 year European study showing no efficacy after two years.

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Often patients are not aware that alternatives exist and are not given fully informed consent on the stimulators. Those risks include increased pain with any invasive procedure in persons with CRPS, paralysis, spasticity, infection, scarring, potential flare into generalized CRPS pain. The fact that these leads are permanent  - they can never be removed – means that person can never undergo MRI scans in future even if they should have cancer or stroke. The leads become scarred into nerve tissue.

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A colleague, a prominent Harvard trained anesthesia pain specialist in practice for 37 years, declines to recommend stimulators or pumps for that reason: there is no long term data proving efficacy.

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Complications of spinal cord stimulators should be published. Perhaps they exist. If anyone has seen them, please advise me. I tend to see the complications or the failures, but those who place them and the corporations that fund them should have a special obligation to study the complications and the long term benefits. Having a spinal cord stimulator does not prevent use of other medication but it may add to the burden of pain to overcome. Nationally there should be an audit of stimulators placed, with patient outcomes including complications and number of revisions made. The risks are too grave not to require this and the cost is too high if there is no lasting efficacy.

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The excerpt below is from a 2003 review on spinal cord stimulation (SCS) for Complex Regional Pain Syndrome. It may be outdated, however Medtronic failed to provide me with any long term studies when requested:

“The use of SCS for the treatment of pain in CRPS (including RSD and causalgia) has been reported in the literature for over 25 years. The consensus opinion from experts suggests that SCS should be considered in the treatment algorithm when conservative or traditional therapies have failed. However, such considerations are not based on reliable evidence generated through well-designed randomized controlled trials. To date, there has not been a systemic evaluation of the existing literature concerning the efficacy of SCS for patients with CRPS.”

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For those interested in coming to San Diego for two week stay, please see information on long distance patients in banner at top of page.

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I hope my patients who have come from long distance who stayed nearby for two weeks will feel free to comment on their experience.

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~~~~~The material on this site is for informational purposes only, and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider. ~~~~~

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I asked an expert, Dr. Ian Zagon

He was very kind to respond

~Dr. I

Dr. Ian S. Zagon is Distinguished Professor of Neural and Behavioral Sciences at The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania.

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His response:

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There are so many misconceptions about LDN that we could spend an hour correcting all of this ancedotal information. The problem is that patients do not read the literature, and offer their “opinions” as if this is true.  LDN is a great example of the good and bad about the internet.

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LDN is an immunosuppressant – it works through the opioid growth factor – opioid growth factor receptor axis

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OGF (LDN) acts as an inhibitor of the cell cycle, increasing p16 and p21 in the cyclin-dependent kinase inhibitory pathway. We are in the midst of writing all of this up for publication. On a practical basis, you would not recommend an immunostimulant to someone with MS or Crohn’s Disease (we just finished a Phase II trial on LDN and Crohn’s right now – worked nicely).

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LDN should be fine for MS – with or without other therapy

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I suspect you will find that you will be tapering your patient off of other therapies very shortly, and having your patient on LDN only.

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Remember – use around 3 mg/day

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Start your patient with LDN daily – try it in the evening.

If there is disturbed sleep, switch to the morning (it will make no difference in efficacy)

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Skip’s Pharmacy in Boca Raton, FL – they are on the web – has excellent LDN (some compounding pharmacies do not use the right bulking agents and the LDN is weak or inactive).

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[PJ's Prescription Shoppe in San Diego makes high quality capsules. And I do at times prescribe a suspension that is easier to adjust doses. The important thing is to use Avicel filler ( microcrystalline cellulose) and do not make SR sustained release capsules....ns]

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I wanted to add that OGF is the real, natural biological peptide and its mechanism is on native physiological processes. LDN is merely a tool to access and take advantage of the OGF-OGFr axis.  There are other ways of taking advantage of this system as well.

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Secondly, OGF and LDN work nicely in combination with chemotherapy as well

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We have a great clinical study going showing that OGF and gemcitabine are a terrific combo for treatment of advanced pancreatic cancer. Patients on OGF alone have lived for 2 years, and right now we have a patient on OGF and gemcitabine who is out around 15 months – and is doing splendidly. We have a paper out on OGF and pancreatic cancer – Phase I. Another study, phase II, is in press in Open Access Journal of Clinical Trials – look for it.

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Another woman, lives close by me, who was an aerobics instructor and has MS, has been taking LDN. She has made a remarkable recovery and is back teaching aerobics. Her family donated $50,000 to our research in honor/appreciation for our discovery, and 8 months later (the other day in fact) she gave us another $50,000. We have a group of researchers now doing the science.

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Dr. Zagon

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Vicki Finlayson and Low Dose Naltrexone

Before naltrexone relieved pain and symptoms of Multiple Sclerosis,

she had used Oxycontin and morphine for a year and a half

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While prescribing low dose naltrexone (LDN) for patients with pain in recent years, I have become deeply impressed with it. Of course, it is inescapable to get very far on the internet without seeing a flood of videos and comments on the use of low dose naltrexone for Multiple Sclerosis. I once spent an entire afternoon reading the literature and watching the videos of patients, doctors, and researchers. How I wish I had the links so I could post them here now! The stories of Dr. Pat Crowley sitting at his desk as his patients in County Kilkenny, Ireland, described the successes they had had with multiple sclerosis touched my heart deeply. Naltrexone is not a cure but its beneficial effects on the immune system have been described here and were first noted by Dr. Bihari in 1985. Dr. Crowley sees results in at least 70% of patients, particularly with neurogenic bladder.

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Vicki Finlayson has had a remarkable recovery from severe Multiple Sclerosis. I hope you will watch her interview here. It was recorded October 2008 at the Fourth Annual LDN Conference held for the first time on the West Coast at the University of Southern California, and is recounted below. Since then she has made it her mission to advocate for clinical trials of this medication but it has been difficult for patients to find doctors who will prescribe it.

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Has medicine come to the point where we no longer listen to patients, only to drug representatives that are only allowed by Congress and the FDA to discuss what has been fully approved with all its risks and benefits? Well….frankly, we are not always told all risks nor are they always discovered until years later. Naltrexone is an opiate antagonist. It will block morphine and similar pain medication. In much higher doses it has been approved for safety by the FDA in 1984 as treatment for opiate addiction, and in 1995, FDA approved for treatment of alcohol dependence. Doctors have been reserved about prescribing it off label for patients who request low doses of naltrexone for medical conditions such as Multiple Sclerosis. But the tradition of using medication “off label” for uses not approved by FDA is still alive. Weighed against the dangers of the illness relative to a small dose of a medication that appears to be benign, it appears to be a worthy endeavor to test.

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How tragic is it to hear a person with Multiple Sclerosis have to define their day in the world by how far apart the bathrooms are when needed for neurogenic bladder? That is the story that urged one Scottish research doctor to pay attention when his patient said low dose naltrexone cured his neurogenic bladder. That changed that doctor’s research career. When years of fatigue and heat intolerance may soon be gone because of this small dose, how can a doctor turn down trying it for a patient? I did a few years ago, to my everlasting regret. I know better now. In my defense back then, I had not heard any information from that patient or anyone about its favorable off label use. It was a call from another doctor. I would like to think that if the patient had made an appointment with me or written to tell me a little about it, I would have said I’d read on the subject.

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Vicki’s Story

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Vicki Finlayson had Multiple Sclerosis for 12 years and was very disabled for several of those years with Secondary Progressive Multiple Sclerosis.

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She tells how she was on Avonex for 6 years that caused flu-like symptoms so severe she was in bed for two days after each injection. She was so disabled her husband had to help her dry her hair. The medications used for Multiple Sclerosis caution about suicide risk and her husband hid knives at night for fear of what she would do to herself. She was unable to work, on medicare and social security disability. She missed the ability to work and says, “I lost so much dignity, I lost my sense of everything my parents ever taught me.”

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She detoxed herself off of opioid medication that had been prescribed for pain. Her doctors failed to help her do that. Apparently, she says, they had no experience with how to take her off those medications. And she began to take low dose naltrexone 4.5 mg. It took away all of her symptoms, including heat intolerance.

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She is delighted to be off of disability and back to work selling durable medical equipment to doctors. And she has been inspired since then to help others by raising money for research on use of low dose naltrexone for Multiple Sclerosis.

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Here is how she did it

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She walked 56 miles from her home in Auburn California to Sacramento in scorching hot 100 degree weather – without any heat intolerance that she had had for years before – to try to get the ear of the governor. She held fund raisers. And she got the attention of Dr. Bruce Cree of the UCSF Multiple Sclerosis Clinic to do the first academic trial on use of low dose naltrexone in Multiple Sclerosis, research which apparently was funded by her efforts. She is indefatigeable in her effort to help others.

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Dr. Cree’s poster presentation on the positive research outcome is here along with other scholarly publications on naltrexone. The publication can be read here: “A rapid on-line publication of the first randomised controlled trial of low dose naltrexone in MS in the Annals of Neurology has been reported prior to hard copy publication. The study randomised 80 people with MS to receive LDN or placebo in a cross-over study where people took the LDN or placebo for eight weeks, then swapped to the other study drug. This appears to be the first drug trial in MS that was not funded by the pharmaceutical industry, but by the participants themselves.”

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He closes with: “In conclusion, in this exploratory, single center study, 8 weeks of treatment LDN was associated with symptomatic benefit with respect to mental health, pain and perceived cognitive deficits in MS. Confirmation of these findings in a multicenter trial will be necessary to make definite conclusions about the possible symptomatic benefit of LDN in MS. A longer duration of treatment is necessary to determine whether LDN has any benefit with respect to physical outcome measures.”

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Here is a link to more clinical trials on low dose naltrexone, and here is a

summary of the first European LDN conference in April 2009 at Glasgow University.

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Vicki is very realistic about the chance of this work being extended by any university, NIH or the National Multiple Sclerosis Society. They rely on tens of millions of dollars to do the costly multi-center long term drug studies that must be done for this condition. That will not happen with a drug that is inexpensive, generic, and holds no promise from which any pharmaceutical company may ever hope to profit. Without such double blind studies, many, if not most doctors would be unlikely to prescribe this simple, inexpensive, low dose medication.

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Please see comments, below, that point to an excellent resource called LDNAware.org. “This website is your worldwide gateway to Low Dose Naltrexone information, resources and events.  LDN Aware is a volunteer group devoted entirely to spreading knowledge and raising public awareness about LDN as a treatment for autoimmune disease, cancer and HIV/AIDS.”

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Should LDN be used with other disease modifying drugs for Multiple Sclerosis?

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In my next post of May 16, 2010, an expert answers that question.

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“Never doubt that a small group of thoughtful committed citizens can

change the world; indeed, it’s the only thing that ever has.”

- Margaret Mead

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The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

Rational Polypharmacy

Naltrexone is a remarkable drug for intractable pain

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I first saw this RN in June 2006.

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She is now 60 years old.  She was an OR scrub nurse for almost 30 years, but was disabled for the last 5 years before seeing me. She had Reflex Sympathetic Dystrophy [RSD] of both legs with “arthritis” of the feet/ankle that felt like she was “90 years old” with cold allodynia. Allodynia is pain from a stimulus such as light touch or a breath or air that is not normally painful. Imagine a light touch that feels like severe nerve pain, one of the most disturbing pains a person could have. The temperature of her feet was 81 degrees, hands 92 degrees.

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Pain of both feet felt like a vise grip, gnawing, penetrating, “like broken bones in the feet,” variable at different times but always worse as the day progressed, with a crushing sensation that penetrated through foot and ankle. She was unable to tolerate socks or anything on her feet after 5 pm, unable even to tolerate air on the area, unable to tolerate coolness below waist, but felt hot above waist. She wore a blanket and covers on the hottest 120 degree days, and forced herself to tolerate touch at the legs in order to desensitize them, as we instruct patients to do. She felt constant tingling numbness of the soles of feet for 3 years, with weakness, stiffness “almost solid” like a block. Spasm in soles of feet had resolved the last 6 months before seeing me.

Pain ranged from 2 to 9 on a scale of 10, where 10 is the worst pain imaginable, worst after 5 pm. Average pain was 3. It interfered with sleep at times, and she used a tented frame to keep blankets off her feet, preheated the bed to avoid any coolness, and avoided cold under all circumstances. In the morning, the joints felt like she had a broken ankle. She would massage the feet with lotion, put on alpaca socks, and slowly begin to walk. Then tried to mobilize the joints. Walking made pain worse though walking had always been a favorite activity.~

Before seeing me she had had more than 10 sympathetic blocks, was hospitalized 11 days due to headache from prednisone 60 mg that had been trialed to relieve her pain. She had been prescribed Procardia to relieve the “vascular” disease that she did not have but the drug led to gangrene of the gall bladder; she had been prescribed almost every “adjuvant” used to relieve pain and as much as 9 grams of Neurontin daily, all of this to attempt to relieve the severe pain in her legs and feet.

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This is how she got better

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When I first saw her in 2006, I prescribed low dose oral ketamine that gave relief lasting up to 3 hours from each dose. She then requested referral to Dr. Schwartzman, chief of neurology at Drexel University in Philadelphia, for continuous 5 day ketamine infusion that was done May 2007. She was pain free but it completely lost effect after 8 months, despite booster infusions every 4 to 6 weeks for 4 hours daily over 2 days during those 8 months. After insurance the cost out of pocket was $45,000 in 2007 alone. Dr. Schwartzman had nothing more to offer after it failed and said most patients have relief for less than 6 months if at all.

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In March 2007, I started her on a combination of Namenda 55 mg daily with lamotrigine 350 mg daily that relieved 90% of the pain, but once every 6 to 8 weeks she needed 12.5 to 25 mg low dose oral ketamine for breakthrough pain. Even more rarely, she used oxycodone 10 to 20 mg.

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In October 2008, adding naltrexone 1 mg by mouth, she became pain free. Since then she has not needed anything for breakthrough pain and on 3/5/09, she reported that her last use of ketamine and oxycodone occurred with the addition of low dose naltrexone.

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In 2009, she hiked 30 miles down the Grand Canyon and back up in 3 days.

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Naltrexone was later increased to 4.5 mg as she completely tapered off lamotrigine.

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By December 2009, the RSD was 98% better and she reported that it was not pain anymore. Medications then were naltrexone 12.5 mg at bedtime and Namenda 55 mg daily in divided doses. She had just a “remnant” of a little buzz, but no crushing except when active, late in the day.

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A few months later she slowly tapered off Namenda with no increase in pain; and in October 2010, on my advice she tapered naltrexone 12.5 mg from daily to every third day. There has been no increase in pain but she is reluctant to discontinue naltrexone for fear that RSD may recur.

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She hikes 2 miles 3 to 4 times a week, does Iron Mountain once a week, does “Silver Sneekers” exercise 1 hour 3 times a week and sleeps well 8 to 10 hours a night without a sleeping pill.

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She remains on low dose naltrexone as her sole medication for this

previously disabling neuropathic pain syndrome~

~

She has returned to part time work and spends a few weeks a month traveling the world, hiking, volunteering, sightseeing.

.

Research funding is needed to view whether we can detect

activated glia in the spinal cord, as discussed here.

If there are no signs of activated glia, she may feel reassured that the condition has resolved.

Naltrexone is an immune modulator.

The site of action of naltrexone is at the Toll-like receptor (TLR4) attached to the cell surface membrane of glia.

The ability to view activated glia would help greatly in treatment of so many conditions including neuropathic pain.

~

Naltrexone

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I have found that naltrexone is a remarkable medication for various pain conditions, and going through the steps of rational polypharmacy may be very rewarding for some patients though at times it may work all on its own. It has caused me to completely reassess how I approach the treatment of intractable pain – not just RSD or CRPS but arthritis, sciatica and various forms of mechanical pain. And it has led to further changes in the timing and dosing of naltrexone based upon the experiences patients have reported back to me over the years. It is hoped that further research will lead to better understanding of how naltrexone acts upon pain pathways. Surprisingly we already know quite a fair amount.

~

My deepest gratitude to Dr. Jau-Shyong Hong, Chief of Neuropharmacology at NIH, whose many generous discussions, emails and research publications have helped me to understand it’s profound anti-inflammatory effect in the central nervous system through its actions on microglia. I previously posted a discussion of mechanisms of naltrexone and dextromethorphan in greater detail here. Naltrexone and dextromethorphan are classified as morphinans, morphine-like. They suppress Superoxide, a free radical that destroys neurons which may cause or contribute to Alzheimers and Parkinsons Disease. That research goes back to the late 1980′s and continues to grow. Phase II studies with morphinans are now being done on those conditions. Studies are also going on now with naltrexone/Wellbutrin combination for weight loss. The drug is called Contrave, from Orexigen Therapeutics Inc. and the dose I believe is 32 mg naltrexone – I do not know how they decided upon that dosage.

~

In my experience, naltrexone is a very benign drug at these low doses, though colleagues who prescribe 400 mg for the FDA approved use at that high dose may see some liver toxicity. I always begin at 1 mg or 4.5 mg, depending upon whether or not the patient is a slow drug metabolizer, i.e. may lack one of the CYP P450 chromosomes for metabolizing drugs. I have long suspected it also has an effect on the hypothalamus because a few patients with profound postmenopausal hot flashes have reported that is no longer a problem and that their husbands simply cannot believe the bonus, and this may explain the effect upon appetite that Orexigen has found. At higher doses than I generally use there may be some constipation which is treatable. It may cause vivid dreaming in some, and a small percentage may have insomnia for a few days. Pharmacology and safety is discussed here.

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Stay tuned. I’ll be adding more case reports of different pain conditions in the near future. They are truly fascinating. It has changed my entire approach to treating pain.

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Cost

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Wouldn’t it be nice if NIH funded more for pain research? Imagine how much money that would save the country and save the lives of each person with disability who could recover? As I posted here, the American Pain Society has shown that NIH spends 0.67% of its budget on pain research – less than 1% – though 10 to 20% of the population in the US suffers from chronic pain, an estimated 60 million Americans, and pain conditions are more prevalent among the elderly.

~

I am told by my pharmacist that perhaps 70% of the time insurance will approve coverage for compounded low dose naltrexone. It is very affordable but some insurance carriers deny payment for naltrexone. Medicare will not pay for compounded medication either. Compare this low cost compound to the wholesale price for 100 tablets of Oxycontin, $1300, which may not be relieving pain – then multiple that by 2 or 3 each month for one patient. Imagine if the $22 billion of federal money for health insurance technology, for software which is untested and will expire in a few years, instead went into NIH funding for pain research. What a lovely thought. 

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The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

~

~

Anti-inflammatory medication — salsalate, from the aspirin family —

helped poorly controlled Type 2 diabetics lower their blood sugar substantially.

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Fasting blood sugar dropped from 150 to 110

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This is a very interesting report of studies being conducted on fat to unlock the mystery of why it triggers inflammation that leads to heart disease and diabetes. Some startling conclusions are arising from these multi-center studies and the news release nicely summarizes them.

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Although the article does not quote the journal referenced, it does discuss the research being done at Albert Einstein College of Medicine as well as the NIH funded study at 21 medical centers around the country that are now recruiting Type 2 diabetics.

You might find out if a center nearest you is recruiting and be sure to discuss salsalate with your treating doctor before you consider trying it.

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The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

~

Thi

Analgesic Use and the Risk of Hearing Loss in Men

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Dr. Sharon G. Curhan of Brigham and Women’s Hospital in Boston and her colleagues studied 26,917 men aged 40-74 years at baseline in 1986 and every two years. These were men enrolled in the Health Professionals Follow-up Study. Regular use of analgesics was defined as 2+ times/week.

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Among all men who used aspirin at least twice a week, there was a 12% increased risk of hearing loss.
Among those who used ibuprofen and related analgesics, there was a 21% increase.
And for those who used acetaminophen, a 22% risk.

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But the risk was much higher when they considered only men younger than 50.

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In that group, there was a
33%  increased risk for aspirin use,
61% increase for ibuprofen and related NSAIDs, and
99% increase for acetaminophen.

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The younger the man and the more years used, the greater the risk of hearing loss.

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The study involved only male Caucasians, thus no conclusions can be drawn on risk of use for women and other racial groups.

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Some supplements can be extremely helpful for conditions I follow in my practice, while others may harm. Go to this constantly updating link to enlarge a brilliant and very useful bubble graph “like painting with data”— or view a static, fixed copy below.

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“This image is a “balloon race”. The higher a bubble, the greater the evidence for its effectiveness. But the supplements are only effective for the conditions listed inside the bubble.” Try it! And when you click to the right of their active link to select a medical condition, it will suggest a supplement that has been shown to help. Then return back here, below the graphic to check on cautions and toxicity that importantly is not mentioned in their work.

As explained for the graph, “This visualisation generates itself from this Google Doc. So when new research comes out, we can quickly update the data and regenerate the image.” The Google Doc is a spreadsheet of references from large human, blind placebo-controlled trials only, sourced from PubMed and Cochrane that publishes leading medical research.

~~

CAUTION: Toxicity is still important. For example, even though licorice is helpful for coughs, it may seriously increase blood pressure. Valerian may help sleep but may be toxic to liver and may have a withdrawal syndrome.

~

Make sure you check here to review the benefits and toxicity to see how supplements may alter your chemotherapy or medication for heart and blood pressure. Another review here: Use of Herbal Products and Potential Interactions in Patients With Cardiovascular Diseases.

The paper lists several common common drug-herb interactions: Grapefruit juice can be especially risky, increasing your dose of statins and calcium-channel blockers by slowing the metabolism of those prescriptions. St. John’s Wort raises blood pressure and heart rate;  garlic and ginger increase the risk of bleeding in patients on blood thinners. Soy milk and green tea can decrease the effectiveness of warfarin. Ginkgo biloba, ginseng, echinacea, aloe vera and licorice are also discussed.~

A recent multi-center, double blind, randomized trial of Ginkgo Biloba involving 3,019 subjects over a median of 6.1 years showed that it fails to help memory. Further, a new report in the Journal of Natural Products summarizes beneficial uses but also discusses toxic effects on heart and brain due to the ginkgotoxin. The authors recommend that sales should be restricted. Toxicity to the heart may occur from heart block, ventricular fibrillation and death. And it may lower the seizure threshold in persons with epilepsy. The toxin depletes vitamin B6 in the brain, impairs glutamate metabolism, and triggers seizures via an imbalance in neurotransmitters: high glutamate and low GABA. It has been shown to induce metabolism of epilepsy medication, thus dropping blood serum levels below therapeutic range further increasing risk of seizure.

Remember to ask your doctor how these may interact with your medication.

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Check here on Vitamin D, a steroid hormone that is anti-inflammatory. Vitamin D is one of the hottest topics in kidney research and hypertension today, as discussed here. And hypertension is important. The latest research on Alzheimers Disease in the last two years from Columbia University Medical School in NYC tells us that risk factors for Alzheimers Disease are the same as for coronary heart disease: exercise, hypertension, cholesterol, obesity, diabetes, smoking. Besides, low vitamin D increases risk of cancer of breast, colon, prostate among many other functions. “Vitamin D insufficiency is associated with suboptimal health.“

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The material on this site is for informational purposes only, and

is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

What you can do

“Moving is the best medicine”

~

For headache and neck and shoulder pain

As reported in the leading headache journal, Cephalalgia, office workers with headache, neck and shoulder pain took part in an education and relaxation program in an Italian study over eight months. They kept diaries and did posture and relaxation exercises every two to three hours. Compared to a control group, headache and neck and shoulder pain decreased by more than 40% and use of analgesic drugs was cut in half.

~

For Arthritis Pain

This is an excellent article from Nature Reviews Cardiology, 18 August 2009, and offers doctors CME 0.75 AMA PRA Category 1 Credits. Click blue link below for complete article.

Vitamin D status and arterial hypertension: a systematic review

Stefan Pilz¹, Andreas Tomaschitz¹, Eberhard Ritz² & Thomas R. Pieber¹

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A short excerpt is included here:

Vitamin D deficiency is common and is primarily caused by a lack of ultraviolet-B (UVB) radiation from reduced sun exposure, and the consequent limiting of vitamin D production in the skin. The vitamin D endocrine system regulates about 3% of the human genome. Observational data support the concept that vitamin D is involved in the pathogenesis of cardiovascular diseases and arterial hypertension. The antihypertensive properties of vitamin D include renoprotective effects, suppression of the renin–angiotensin–aldosterone system, direct effects on vascular cells, and effects on calcium metabolism, including prevention of secondary hyperparathyroidism. The results of clinical studies largely, but not consistently, favor the hypothesis that vitamin D sufficiency promotes lowering of arterial blood pressure. Randomized, placebo-controlled trials are greatly needed to clarify and definitively prove the effect of vitamin D on blood pressure. In general, the antihypertensive effects of vitamin D seem to be particularly prominent in vitamin-D-deficient patients with elevated blood pressure. Thus, in view of the relatively safe and inexpensive way in which vitamin D can be supplemented, we believe that vitamin D supplementation should be prescribed to patients with hypertension and 25-hydroxyvitamin D levels below target values.

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Vitamin D metabolism

In humans, the primary source of vitamin D is UVB-induced conversion of 7-dehydrocholesterol to vitamin D in the skin.¹ Just 10–20% of our vitamin D comes from dietary sources, such as fish, eggs, or vitamin-D-fortified milk (Figure 1).¹ Vitamin D is hydroxylated in the liver to 25(OH)D—the main circulating vitamin D metabolite, which is largely bound to vitamin D binding protein in serum, and is used to classify vitamin D status: vitamin D sufficient (25[OH]D 30 ng/ml [or 75 nmol/l]), vitamin D insufficient (25[OH]D 20–30 ng/ml [or 50–75 nmol/l]), and vitamin D deficient (25[OH]D <20 ng/ml [or <50 nmol/l]).¹ These cut-points are currently the most commonly used classification of vitamin D status, but some debate about exact threshold values still exists. Some researchers consider 25(OH)D levels of 10–20 ng/ml (25–50 nmol/l) as vitamin D insufficient and levels below 10 ng/ml (25 nmol/l) as vitamin D deficient, whereas others use a cut-off level of 40 ng/ml (100 nmol/l) to define sufficient vitamin D status.^{9, 10} 25(OH)D is transformed by renal or extrarenal 1-hydroxylase into 1,25-dihydroxyvitamin D (1,25[OH]2D), which circulates at much lower serum concentrations than 25(OH)D, but has a much higher affinity to the vitamin D receptor (VDR).¹¹ Serum levels of 1,25(OH)2D are mainly determined by renal 1,25(OH)2D production, which is closely related to calcium homeostasis, and is upregulated by parathyroid hormone, the concentration of which increases when calcium levels are low.^{1, 12} In addition, other factors such as fibroblast growth factor 23 and Klotho, which suppress 1-hydroxylase expression, have also been shown to regulate the renal conversion of 25(OH)D to 1,25(OH)2D.¹³ Studies have, however, shown that many other cell types, including those of the vascular wall, express 1-hydroxylase with subsequent intracellular conversion of 25(OH)D to 1,25(OH)2D, which exerts its effects at the level of the individual cell or tissue before being catabolized to biologically inactive calcitroic acid.^{1, 12, 14} These intracellular tissue levels of 1,25(OH)2D are determined by the concentration of circulating 25(OH)D, which is, therefore considered the best indicator of whole-body vitamin D status. Importantly, extrarenal 1-hydroxylase expression also underlies various regulatory mechanisms. In this context, extrarenal 1,25(OH)2D production in macrophages is stimulated by Toll-like receptor as part of the innate immune response against intracellular bacteria.¹⁵ Another example of extrarenal regulation of 1-hydroxylase is the increased production of 1,25(OH)2D by keratinocytes in wounds, which could be induced by transforming growth factor 1.¹⁶ 25(OH)D serum levels, therefore, provide a good estimate of vitamin D status, but regulation of 1-hydroxylase activity should also be considered.

1,25(OH)2D binds to the VDR and, after forming a heterodimer with the retinoid X receptor (RXR), binds to specific DNA sequences—the so called ‘vitamin D responsive elements’. These sequences are located in the promoter regions of various vitamin-D-dependent genes that are either upregulated or downregulated by the RXR–VDR complex.^{1, 12, 14} Approximately 3% of the human genome is directly or indirectly regulated by the vitamin D endocrine system, which supports the idea that vitamin D insufficiency has widespread adverse consequences for human health.¹⁴ In addition to cardiovascular pathology, vitamin D insufficiency can cause musculoskeletal, malignant, metabolic, or immunological diseases.^{1, 12, 14}

…..

Vitamin D Anti-hypertensive effects

(click link for slide)

…..

…

*25 percent of households have trouble paying

*40 percent expect to delay care this summer

*Baby boomers hardest hit

“The percentage of households that had difficulty in paying for care in the last year was statistically unchanged between March and April (about 25 percent).”

They found 40 percent of all households planned to postpone care in the coming three months, with about 15 percent planning to put off routine doctor visits.

Baby Boomers were four times more likely than seniors to have trouble paying for healthcare, according to the report.

Not surprisingly, those on Medicare “were the least likely to delay care.” Youth were also less likely, probably because they have fewer health problems.

New Poll Shows 76% Support For Choice Of Public Plan

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Excerpts from the Huffington Post summary:

New poll numbers from NBC/Wall Street Journal produce two major and potentially conflicting story lines when it comes to the Obama administration’s efforts for a health care overhaul.

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• 76 percent of respondents said it was either “extremely” or “quite” important to “give people a choice of both a public plan administered by the federal government and a private plan for their health insurance.”

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• [O]nly 33 percent of respondents said they thought the president’s health care plan, to the extent they knew of it, was a “good idea”

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• But when read a description of the general outline — requiring insurance companies to cover pre-existing conditions, an employer mandate, tax credits for lower income families to buy coverage, and tax increases on wealthier Americans to pay for it – the number of respondents in support rose to 55 percent.

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Public option is not Single Payer. People know that “For profit” is not “For them.” Only a single payer plan such as Medicare lifts the burden from small and large business, puts people first over profit, and cuts out the middle men that crush the country’s financial future. It’s not perfect, but there is no rescission of coverage, no denial for pre-existing conditions, no inequality.

For all the denials from your PPO and the unaffordable medications you cannot receive, how many billions do insurance companies and pharmaceutical firms pay for advertising? Do you think your rates will stay the same if you had cancer or some critical illness that cost hundreds of thousands of dollars? How many months would you have to wait to get disability coverage? How much competition would there be for the shrinking public dollar then as the population expands and more need the same helping hand? Healthcare identity theft is increasing at a startling rate. If someone stole and used your insurance, as it now stands, your insurance company would hold you responsible for the hundreds of thousands of dollars of care they received. This black market would not exist if we had Single Payer insurance.

A fellow I know from England says that whenever anyone had a complex problem, they knew they’d get better care at the National Health Service Hospital, even though they could easily afford private care. Doctors there could participate in both plans. Private patients who paid more would be seen first, and others would wait to be seen as time permitted.

Before this all hardens into cement and we are stuck with business as usual and uncompromising profiteering, Robert Reich explains: How Pharma and Insurance Intend to Kill the Public Option, And What Obama and the Rest of Us Must Do.

Test yourself to see how difficult the decision is.  The Price of Life: When Healthcare Meets Money. Ask who would you want making these difficult decisions? A a select panel of expert physicians or Big Insurance? From COMMENTS on the article:

I don’t mind commenting on this subject.

The ‘Price of Life’ from a scientific or Human perspective:

If viewed from the drug manufacturer’s perspective, then it would be economic; return on investment.

But they have no power as to the availabililty of the product, except to the minority of patients who can pay. Not economically viable.

The target therefore, is private health organisations or health trusts

Whilst the former surely has the ability to pay, directly or from health insurance, they will still make up only a minority of the target population this drug was intended for.

The economics of research, development, manufacture and distribution must reflect the true target: Government funded health-care.

This was the intended target from the beginning. And it is based on guilt, an emotion large Corporations generally don’t feel.

The marketing fact is, ” We have invested an enormous amount of capital in a drug that never before existed, and if you can’t or refuse to provide this new medication, then it is you who must bear the consequences.”

Meaning criticism and real life consequences.

So, the guilt remains with the provider, and the carer. NOT the developer.

Limited resources, and TRIAGE.

The big Pharmaceutical Companies have access to the enormous funds required to develop new drugs.

But the balance between who pays and who benefits will be a major obstacle, until a public funded organisation can provide a similar service for free.

ISN’T THAT WHY WE ARE SCIENTISTS?Are we doing it for the money, or from intellectual morality?

You know that without Single Payer, Big Insurance will be making the decisions and you may lose your life, only their decision will be weighed against their profits.

Either way, unless you are independently wealthy, someone must make the hard choices. Unlimited cost is not a choice that can go on indefinitely. We’ve come to the end of the money line. We are paying top dollar for two wars, for worldwide economic crises brought on by mass greed and theft, and Big Insurance and Big Pharma want things to benefit them, not you, just like it always has. The public does not have a chance against their wealth and influence over Congress.

Game over before it begins. I can’t wait to hear laughter on the end of the line next time my patient’s medication is denied.

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Posted in Controversy, Insurance, Politics of Pain Tagged: Public Health Insurance ]]> http://painsandiego.com/2009/06/18/new-poll-shows-76-support-for-choice-of-public-plan/feed/ 1 painsandiego cement truck believerjerk http://painsandiego.com/2009/06/17/md-haunted-by-the-dirty-work-of-managed-care-ppos-that-deadly-piece-of-paper-denied/ http://painsandiego.com/2009/06/17/md-haunted-by-the-dirty-work-of-managed-care-ppos-that-deadly-piece-of-paper-denied/#comments Thu, 18 Jun 2009 06:22:48 +0000 Nancy Sajben MD http://painsandiego.com/?p=2065 ]]> ·

“I know how managed care maims and kills patients”

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I will never forget the snarly laughter of a “medical” reviewer two weeks ago as he denied medication to my patient that the same PPO had been authorizing for years. My patient has been haunted by the man’s laughter since then. Denial of continuing medication is happening more and more despite California law that “grandfathers” in ongoing care for previously covered medication. See my post here.

It is “DESUETUDE.” It refers to the condition where a law has gone unenforced for so long that it is considered ‘obsolete.’ The law has not been repealed, but — here’s the clincher — the law has “collapsed into unenforcibility.” (quote from William M. Lamers, Jr, MD)

For years we have had spreadsheet medicine: Denial only for medication that is costly. It’s getting worse, more brazen.

Now that much new medication is unaffordable, priced far beyond the rate of a decade of inflation, what do we do with lawmakers that will not negotiate volume discount prices with pharmaceutical companies? How long will the middle class be able to afford common medication?  There isn’t another first world country on the planet that does not negotiate volume pricing.

Why are safe older pain medications being taken off the formulary?

Did you know that prices on best selling medicines may go up as much as 20 to 30% each year, though they’ve been on the market for years?

What is worse, managed care bloodlessly denies life saving procedures. A bloodless coup that rarely makes the news.

Physician Confesses to Congress, Choking Back Tears

Dr. Lynn DiPino [spelling?], former medical reviewer for Humana went before Congress to make “a public confession.”

This doctor, who acted as a reviewer for an insurance company, denied life saving surgery for a man and thus caused his death, saving “the company half a million dollars.”

Her decision to deny surgery insured her continued advancement in healthcare. “I went from making a few hundred dollars a week as a medical reviewer to an escalating six figure income as a physician executive.” “I was told repeatedly I was not denying care, I was simply denying payment. I know how managed care maims and kills patients. So I am here to tell you about the dirty work of managed care.”

As the video continues on the origins of managed care, it goes back to February 17, 1971, when Ehrlichman discusses Kaiser HMO with President Richard Nixon : “All the incentives are for less medical care because the less care they give, the more profit they make.”

Nixon smiles, his eyes narrow as if he is savoring fine wine, and says, “Not bad.”

Health Insurers Refuse to Limit Rescission of Coverage

withering criticism from Republican and Democratic Congress members

Today in Los Angeles Times

Even Republicans were appalled when “[e]xecutives of three of the nation’s largest health insurers told federal lawmakers in Washington on Tuesday that they would continue canceling medical coverage for some sick policyholders, despite withering criticism from Republican and Democratic members of Congress who decried the practice as unfair and abusive….

An investigation by the House Subcommittee on Oversight and Investigations showed that health insurers WellPoint Inc.[parent of Blue Cross of California], UnitedHealth Group and Assurant Inc. canceled the coverage of more than 20,000 people, allowing the companies to avoid paying more than $300 million in medical claims over a five-year period.

It also found that policyholders with breast cancer, lymphoma and more than 1,000 other conditions were targeted for rescission and that employees were praised in performance reviews for terminating the policies of customers with expensive illnesses.

("Um . . I know this is a bad time but . . . .you're not covered.") shamelessly stolen from crooksandliars.com

…Rescission was largely hidden until three years ago, when The Times launched a series of stories disclosing that insurers routinely canceled the medical coverage of individual policyholders who required expensive medical care.

…A Texas nurse said she lost her coverage, after she was diagnosed with aggressive breast cancer, for failing to disclose a visit to a dermatologist for acne.

The sister of an Illinois man who died of lymphoma said his policy was rescinded for the failure to report a possible aneurysm and gallstones that his physician noted in his chart but did not discuss with him.

The committee’s investigation found that WellPoint’s Blue Cross targeted individuals with more than 1,400 conditions, including breast cancer, lymphoma, pregnancy and high blood pressure. And the committee obtained documents that showed Blue Cross supervisors praised employees in performance reviews for rescinding policies.

One employee, for instance, received a perfect 5 for “exceptional performance” on an evaluation that noted the employee’s role in dropping thousands of policyholders and avoiding nearly $10 million worth of medical care.

…Late in the hearing, Stupak, the committee chairman, put the executives on the spot. Stupak asked each of them whether he would at least commit his company to immediately stop rescissions except where they could show “intentional fraud.”

The answer from all three executives:

“No.”

Rep. John Dingell (D-Mich.) said that a public insurance plan should be a part of any overhaul because it would force private companies to treat consumers fairly or risk losing them.

“This is precisely why we need a public option,” Dingell said.

…In November 2007, The Times reported that insurer Health Net Inc. paid bonuses to employees based in part on their involvement in rescinding policies. According to internal corporate documents disclosed through litigation, Health Net saved $35 million over six years by rescinding policies.

The disclosures in part led an arbitration judge to levy $9 million in damages against Health Net in a case involving the company’s rescission of the policy of a woman diagnosed with breast cancer.

At the time, Blue Cross told The Times that it did not link employee performance reviews to rescission. Blue Cross also said at the time that it had conducted audits to ensure that claims reviewers were not given any “carrots” for canceling coverage.

The company reiterated that position Tuesday in spite of the committee’s disclosure of two employee performance evaluations from 2003 discussing rescission levels and savings.

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Gene Wilder

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Gimme Some Money

by Spinal Tap

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Chronic use of opioid pain medication

causes molecular and genetic changes that result in pain

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A brief update

American Pain Society May 2009 Symposia: Anti-analgesic Effects of Mu-opioids: Molecular and Genetic Mechanisms

The clinical benefits of opioid analgesics have not been fully realized due to substantial side effects, which include tolerance, dependence and opioid-induced hyperalgesia. Although the precise molecular mechanism of these phenomenon is not understood yet, it is generally thought to result from cellular excitatory effects of mu-opioids which contrast the major inhibitory effects.

Mark Hutchinson, PhD, discussed the new discovery that every clinically relevant class of opioid analgesics non-stereoselectively activates glial cells through TRL4 receptor. Activation of this receptor, primarily expressed by microglia, leads to the release of proinflammatory mediators that counter-regulate acute opioid analgesia.

How can opioid-induced glial activation oppose & augment different aspects of opioid action?

Opioid analgesia is opposed by opioid-induced spinal glial activation since increased neuronal excitability leads to elevated nociception. Increased brain opioid-induced glial activation also leads to increased neuronal excitability & within reward & dependence centers this is believed to increase opioid reward & dependence. Therefore analgesia is decreased & reward/dependence is increased.

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Counteracting hyperalgesia with naltrexone and dextromethorphan

In summary, Dr. Hutchinson describes the TRL4 receptor where opioids act to induce activation of microglia, releasing proinflammatory mediators that counteract analgesia and produce more pain.

Naltrexone, a mu opioid antagonist, has profound anti-inflammatory effects centrally on the microglia to produce analgesia.  This mechanism of action of low dose naltrexone is discussed here.

Dextromethorphan acts centrally on microglia by the same mechanism, producing analgesia.  Both naltrexone and dextromethorphan are classified as morphinans, morphine-like.·

More is less:  increasing the dose causes pain.

A steep road to climb, much less to understand.

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Persistent pain has a prevalence of 1 in 5 of the population

at an annual cost of $1.85 billion per 1 million population.

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Does Pain Management Have a Place in American Healthcare?

Pain focused courses foster affective awareness and shape values formation in medical learners.

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Symposium on Pain Management Aimed at Medical School Students

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Yale’s Medical Bulletin, Published: May 16, 2008

New Haven, Conn. — Physicians-in-training learned about an important aspect of patient care — pain management — at a symposium held recently at the Yale School of Medicine.

In recent years, pain has been designated as one of the vital signs indicating a patient’s well-being by the Joint Commission on the Accreditation of Healthcare Organizations, and pain management is being widely accepted as a basic human right. Yet only 3% of the nation’s medical schools, including Yale, currently have a separate course in pain management. [emphasis mine]

As a first step in its efforts to include separate training in pain management as part of its curriculum, the School of Medicine recently hosted the inaugural Yale Multidisciplinary Pain Management Symposium. The event was organized by student Ninani Kombo under the guidance of faculty adviser Dr. Nalini Vadivelu, associate professor of anesthesiology, with support from the medical school’s Offices of Education and of Student Affairs, as well as the Graduate Professional Student Senate.

The symposium featured presentations on “Pain Pathways,” “Clinical Perspectives in Pain Management,” “Interventional Pain Management,” “Psychology and Pain Management” and “Legal Considerations of Pain Management.” The speakers included Vadivelu, Dr. Sam Chung and Dr. Raymond Sinatra of the Department of Anesthesiology; Dr. Michele Johnson of the Department of Interventional Radiology; Layne Goble, a psychologist at the West Haven Veterans Hospital; and Robert Burt, the Alexander M. Bickel Professor of Law at Yale Law School.

Two physicians also brought in patients so the students could talk with them and learn more about their personal experiences and challenges in living with chronic pain. One, who suffers from migraines, is a patient of Dr. Bahman Jabbari, professor of neurology; and the other, who has sickle cell anemia, is a patient of Dr. Thomas Duffy, professor of internal medicine and hematology.

Plans call for the symposium to continue as an annual event, and to be included within the neurology module of the second-year medical curriculum.

“This will continue to be a multidisciplinary pain symposium and in true Yale medical school tradition it will be organized by medical student volunteers,” says Vadivelu, who will continue to serve as faculty adviser for the initiative. “In the near future, the pain management curriculum may be expanded to include didactic case studies in pain management during the third and fourth years of medical school.

“This commitment,” she adds, “makes Yale School of Medicine one of the leaders among U.S. medical schools in formal pain management education.”

PRESS CONTACT: Office of Public Affairs 203-432-1345

A letter from Yale professors April 2009, to the Editor of the Journal of the Association of American Medical Colleges

The Urgent Need for Pain Management Training

Vadivelu, Nalini MD; Kombo, Ninani; Hines, Roberta L. MD

To the Editor: Approximately 50 million people in the United States suffer from persistent pain,¹ and pain treatment cuts across most medical disciplines. Despite huge strides in understanding pain, there is a major gap between that understanding and pain diagnosis and treatment. In the 21st century, pain management is being accepted as a basic human right.² Thus, it is even more important to train medical students to be competent in the areas of pain assessment and treatment. However, few physicians graduating from U.S. medical schools have had comprehensive multidisciplinary pain education as part of their medical school curricula. This was shown in an AAMC survey in 2000-2001, which found that only 3% of medical schools had a separate course in pain management in their curricula¹; the situation is not much better today. [emphasis mine] Although a free, Internet-based CD-ROM textbook on pain was developed for medical students in 2003 by the American Academy of Pain Medicine, we feel there is an urgent need for formal pain management training within the medical school curriculum.

Pain education in medical schools could be in the form of pain symposiums, pain workshops, lecture series, and clinical rotations in pain management, according to what is available and feasible in each school. Interinstitutional elective rotations in pain management and summer research projects with resulting research publications in pain should also be encouraged. Funding for the latter is available from, for example, Foundation for Anesthesia Education and Research grants to medical students from the American Society of Anesthesiologists. We at Yale have incorporated formal pain education into our curriculum using a multidisciplinary pain symposium at the second-year level with case studies for third- and fourth-year students.

We believe that medical schools worldwide should establish formal pain management education in each year of their curricula. [emphasis mine] This will enable graduating physicians everywhere to be well equipped to ease their patients’ pain.

Nalini Vadivelu, MD

Associate professor, Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut; (nalini.vadivelu@yale.edu).

Ninani Kombo

Fifth-year medical student, Yale University School of Medicine, New Haven, Connecticut.

Roberta L. Hines, MD

Professor and chair, Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut.

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

The War on Drugs Sold so Well That Persons With Pain

Often Cannot Get Pain Medication or Treatment

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Don’t read this. It will upset you.

The federal government has always been more interested in addicts than in persons who are disabled with intractable pain. Billions are spent to imprison addicts rather than pay for addiction programs which would be far less expensive.

Only 3% of medical schools have a course in pain management, Yale announced in 2008. According to the International Association for the Study of Pain, the IASP, education on pain is poor “at either the preclinical or clinical levels and information is poorly integrated.” Fewer than 3% of recent graduates have had a few hours of training. This means that unless your doctor is among that small 3% that has recently graduated, they have had no training in pain control. None. And the FDA ignores the extensive training of pain specialists when approving limitations on new medications.

Worst of all, NIH spends 0.67% of its budget on pain research – less than 1% – though 10 to 20% of the population in the US suffers from chronic pain, an estimated 60 million Americans, and the conditions are more prevalent among the elderly. Addiction funding is the only reason neuroscientists in the early 1970′s were able to identify opioid receptors and then to clone them, which legitimized pain in cancer patients and led to use of opioids for cancer pain in the 1970′s and for noncancer pain in the 1990′s.

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Pain Epidemic:

Does Pain Management Have a Place in American Healthcare?

Today, there is too much reliance on opioids for pain because there is little or no NIH research on alternatives. Or maybe because your doctor does not know any other treatment than to prescribe an opioid. Or because Medicare will not pay for the amount of physical therapy you need. Opioids are overprescribed. This increases the risk of opioids being diverted and falling into the hands of addicts, leading to deaths and headlines that will no doubt limit your ability to be treated for pain. How many of you know Medicare has been limiting physical therapy for years? If you use all your treatment by mid February, they will not pay for more no matter how often you fracture your hip or herniate a disc. Is it right for them to pay for opioid pain medication and not physical therapy?

Just think of it. Before the early 1970′s, we had no pain societies, no hospices, no use of opioids for cancer patients (unless they happened to be hospitalized), no oral opioids, no oral morphine — why the very thought that oral morphine could work was argued against vehemently by the chief of the pain service at Memorial Sloan Kettering Cancer Center in NYC, in December 1975 at the first meeting of the IASP. The first meeting. 1975. Think of it. He argued that oral morphine would be metabolized so rapidly that it would pass out of the body and not be there to help.

William M. Lamers, Jr., MD

In the early 1970′s if you had pain, you were not legitimate because we simply did not know there were such things as opioid receptors nor did we have oral opioid medication.

Now re-imagine that vehement argument in 1975 again, knowing that my dear friend William M. Lamers, Jr., MD, was the first in the world to use oral morphine when he founded home hospice in America 5 or 6 years before that date. He invited Dr. Cicely Saunders to California to teach her how to use oral morphine at her hospice, and following that, St. Christopher’s Hospice in London stopped using the ineffective Brompton’s Cocktail that caused so many side effects with so much less pain relief. Their research a few years later enabled Dr. Robert Twycross from St. Christopher’s Hospice to stride to the stage in 1975 at the IASP meeting, and report their work with oral morphine, to the applause of the Brits.

Let me be clear, I am gravely concerned that the use of opioids for nonmalignant pain will lead to a dire problem with opioid induced hyperalgesia in our large population of pain patients. If not hyperalgesia, the benefit of relief is undercut by the pain they create as shown by recent research on glia. Opioids create pain at the same time they relieve pain.

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We Are Not Getting Access to Effective Nonopioid Treatments

Worst of all, unless opioids are low cost, your insurance – PPO, Medicare, Medicaid – will not authorize several profoundly important nonopioid medications that help and/or relieve intractable disabling pain in many of my patients:

• Namenda an NMDA antagonist that was shown in European research in 2001 to be effective for severe pain at a dose of 55 mg per day; in the US it is approved only for dementia at a dose of 20 mg per day. Insurance will not cover the dose needed; patients cannot afford it.
• Compounded capsules and ointments may be the only thing that helps others, but are often not approved.
• Naltrexone and other morphinans – see my post on naltrexone -  may relieve disabling pain, but compounded medications are often not approved
• Medical marijuana research has been forbidden by the federal government despite active research and use of approved compounds in Canada and UK for severe intractable pain. Marijuana is in a class of chemicals called cannabinoids. Our brain makes cannabinoids and has receptors where they act. A synthetic cannabinoid  is FDA approved in the US for chemotherapy induced vomiting. The cost of one mg capsules is $400 for 20 – who can afford that?  In Canada, it is used for pain patients at bedtime to relieve severe pain that prevents sleep. Yet in California where inexpensive medical marijuana is legal, the Obama Department of Justice has continued the prosecution of Charles Lynch, a legitimate marijuana dispensary owner.  He was convicted on federal drug charges despite carefully following state and local law in setting up and running his business and being fully licensed by the state. He had the full support of the mayor and city council, yet he was sentenced to a year and a day in jail last week – the Obama DOJ pushed for a mandatory 5 years jail. Federal law prevented him from testimony in his own defense, presumably because federal law excludes states rights and the issue that marijuana sales may interfere with interstate commerce. For discussion of this and the bill introduced Thursday by Rep. Barney Frank, HR 2835, to legalize medical marijuana, see here. There was a time in the recent past when hospice doctors in the US made marijuana suppositories to relieve severe pain and nausea in dying cancer patients. In Mexico, marijuana is used in ointments by the elderly to relieve arthritis pain. 100 years ago, it was mentioned in some medical textbooks in America. And U.S. Rep. Mark Kirk calls for 25 years in prison for first time trafficking offense.
• Marijuana: Effective for severe pain, safe, nontoxic, inexpensive and illegal.
• The legal status of prescribing as well as the legal status of using marijuana is needlessly complicated. The Federal Government is clear… prescribing and use are both criminal offenses. Nothing is for certain except that the legal status is a mess.
• Unrelieved suffering leads to an intensification of pain that may result in depression, withdrawal, irritability, anger and sometimes even hostility to caregivers.

NSAID –  nonsteroidal anti-inflammatory drug – use is discouraged in the elderly.  NSAIDs pose severe risk to the elderly and cannot be used in others due to heart disease, gastric intolerance, ulcers, GERD, anemia, bleeding, kidney disease, asthma, and those who are on various medications such as Plavix or Coumadin. Further, heavy NSAID use leads to higher dementia risk (see my post on this).

Some nonopioid alternatives cannot be used in those with liver or kidney conditions, men over 50 who still have a prostate, persons who wish to avoid suddenly becoming obese (Lyrica), those with allergies or intolerance to their side effects because the drug makes the fall backwards or suppresses their bone marrow.

Worse than those issues, we have only a few opioids which work on specific opioid receptors, some are more specific for neuropathic pain or for allodynia, yet since September 2008, the FDA has removed several of the older opioids from the shelf with no reason given to pharmacists or MD’s. I have spent hours calling pharmacies to see if they stock a medication I wrote for a patient hours before they left the office holding their specialized prescription. You know very well that if a patient called asking about opioids in stock they’d be looked upon as an addict, and many pharmacies will not stock opioids with the excuse they would be robbed. No matter you are in severe pain, you must wait 72 hours until they stock it. 

Even with insurance, your PPO will not authorize many if not most of the medications I prescribe and the cost of medication is surely the #1 reason.  That is true for opioids and nonopioid medication I use for pain control. Many are off label for pain, others are off label for anyone  who does not have cancer despite severe disabling pain, therefore not covered. If you are wealthy, you can purchase any medication prescribed.

Opioids are a distinct issue and outrageously expensive compared to the pennies cost of the raw drug. There is never a discussion of reducing costs of new drugs. Imagine $45 per unit, used 12 or 20 times per day in extreme, rare cases. Then imagine your PPO allowed prior authorization for 1 year, but then it was 6 months, then 2 months. What will happen next month? Hours and hours of non-reimbursed physician time is spent on these.  They could just save us all time if they published a list telling us what they will never ever ever reimburse no matter what. No wonder a radiologist or cardiologist or a doctor who does procedures makes millions every year. They don’t have to deal with the deafening “no.” The California law is never enforced that guarantees continuation of medication that is being used and that has been approved in the past for years. Requesting an independent appeal is a sham, the fox guarding the henhouse, paid by the same company that refused authorization.

The FDA has limited use of short acting fentanyl to cancer pain, thus PPO’s will often not authorize it without a cancer diagnosis.  News flash: there is no such thing as cancer pain. Patients without cancer have the same categories of pain that you do: involving abberent signals from nerve, viscera or other tissues. At the American Pain Society’s annual meeting in San Diego, May 2009, an FDA official admitted there were only 3 pain specialists on a panel of 11 MD’s that reviewed short acting fentanyl. It is likely the other 8 had no training in use of opioids.  Fewer than 3% of medical schools spend less than 30 hours over 4 years teaching pain management to medical students, and that is only in recent years, which means almost all physicians in practice today have had no training in use of opioids. Oncologists included. Do they think that pain specialists who have spent decades in the field have no understanding of opioids? If so, then why do they not limit all strong opioids to persons with cancer? or is this coming? Politicians do not like headlines about addicts who overdose themselves.

The special case of Subutex and Suboxone which is buprenorphine alone or with naloxone. Buprenorphine is an old drug, a long acting opioid that has unique effect at kappa opioid receptors and it is said it may help allodynia better than other opioids. PPO insurance will not authorize Subutex (buprenorphine) for my patients with pain, or if they do, they will authorize only one of the two, Subutex, but not the other, even though the one they will pay for causes intractable migraine but not the other. In Europe, both are approved for pain or for addiction, just like we use methadone here.  But our FDA has limited use to addicts, though it is an important opioid that we might use for pain. This means PPO insurance will not pay for it. This new formulation of Suboxone or Subutex in a sublingual tablet means it is very expensive, and I have patients in pain, weeping that they cannot afford it and must go back on their Oxycontin that works less well.

Unique issues for oral short acting fentanyl and Subutex or Suboxone: both will absorb directly in the mouth which is important for some persons with colitis, abdominal surgery, bariatric surgery, other conditions with poor GI absorption of tablets such as celiac disease, and those who are unable to use fentanyl patches due to skin allergies.

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Need for Balance between Risk of Substance Abuse

vs  Suffering and Disability Caused by Untreated Pain?

The FDA and Congress voice concern about addiction, but how much do they care about pain? Actions speak louder than words and the lack of NIH funding for pain research is shocking. Pain does not make newspaper headlines though pain is the #1 reason people seek medical help, more so as the population ages.

Here are more policy and headline issues that will make it harder for people with pain to get the care they need:

FDA, Pain Docs Look to Cut Abuse of Pain Killers“FDA said it was working on a plan to make it tougher for people to abuse certain prescription painkillers….” From the comments: “Regardless of great efforts to reverse this trend, physicians who legitimately prescribe opioids for pain may still feel ‘damned if they do and damned if they don’t.’ It seems as though we have simultaneously raised consciousness of the need for pain control and increased the risks to physicians of being part of the solution. If this dilemma is not resolved, advancing the cause of pain management as a fundamental human right may, in part, serve to polarize the medical community.”

F.D.A. to Place New Limits on Prescriptions of Narcotics “This is going to be a massive program,” according to Dr. John K. Jenkins, director of the F.D.A.’s new drug center.”  ”…a law passed in 2007 gave the agency a new, intermediate weapon — Risk Evaluation and Mitigation Strategies. Known as REMS, these programs allow the agency to place strong restrictions on the distribution of certain drugs.”

Increased Scrutiny of Opioids Could Alter Prescribing Practice “If a formal risk reduction plan for opioid painkillers increases the regulatory burden on physicians, they may simply stop prescribing such drugs, to the detriment of patients in severe pain, the FDA was told Thursday.” Most physicians have no training in pain management, yet instead of requiring more education, regulation of doctors makes it harder to treat persons with legitimate pain and may have no effect on addicts and illegal diversion that they are really trying to regulate. Suggestions were made at a public hearing, quoted here:

• If a REMS does end up imposing requirements on physicians, positive incentives should be put in place to fund and support training in pain management, such as waiving or reducing the fee clinicians now must pay to the DEA for the privilege of prescribing Schedule II drugs
• But clinicians do not currently have the tools to enforce proper distribution and use of narcotics, and need more support and training, said Jennifer Bolen, founder of the Legal Side of Pain and the Pain Law Institute. ”It’s dangerous and irresponsible to use physicians to teach the law,” Bolen said. She said state medical licensing boards, health insurance plans, and law enforcement officials must play a big role in enforcing the REMS.
• But the FDA is not a criminal enforcement agency, said John Jenkins, M.D., director of the Office of New Drugs at the FDA.
• One suggestion from a number of speakers is that the FDA require opioid manufacturers to put serial numbers or microchips in opioid tablets, linked to the prescription that released them to a patient. That way, if law enforcement officials seize pills, the prescriber and patient can be easily traced.
• The FDA is already considering serial numbers on some classes of medication for a different reason — to confirm the integrity of the supply chain.
• Other speakers suggested creating opioid medications that are “less abusable” such as crush-proof pills. However, formulations intended to thwart abuse have been tried before. That was the original intent behind Oxycontin, the brand of extended-release oxycodone that ended up widely abused.While it’s up to the FDA to decide what a REMS will look like, it’s the responsibility of drug companies to enforce the new regulations.
• the two-day hearing was peppered with emotional testimonies from people whose family members overdosed on opioid drugs that they obtained illegally.
• the FDA might convene an advisory committee before any REMS is finalized.

Addiction is a very important issue. Families are best in a position to see what is happening to members who have addiction problems, but addiction programs are poorly funded and many Americans are uninsured, especially the young who are most vulnerable to chemical dependency. Can families help someone who does not want to be helped?

I want to make it very clear that all of us, myself included, are responsible for reducing addiction, misuse of prescription drugs, and diversion in this country. Yes, that means anyone who gives someone else a pill from their prescribed medication, no matter how harmless it may seem. If that is a pain drug, your pain specialist can go to jail for 30 years even if he or she did not know about it. Never give one of your prescription pills to anyone else.

Designing high tech remedies to prevent opioid tablets from being injected or inhaled by addicts will increase the cost of your pain medication.  It is already difficult to afford without new technology, and why is it so expensive since many are now old drugs and the raw material costs pennies?

If we become disabled or develop chronic pain, there is often no money for the multidisciplinary approach to pain management that is essential for treatment: extreme limits on physical therapy, no cognitive behavioral therapy, no coverage at all for many medications that I prescribe. Some of my patients who are still working are afraid they will be laid off at work if they limp, are slow or show they have pain. This is not unlike my cancer patients who fear public knowledge they have cancer. But the rising insurance cost to their employer is Darwinian evolution at its cruelest, untouched by the human mind and heart. Free for the rich, for profiteering off the most vulnerable.

Cost of high tech pills to deter addicts. We thank the FDA for their guidance in requiring opioid manufacturers to make it more difficult for addicts to abuse these drugs, but does the cost of that new technology make these medications unaffordable for the average person, especially the disabled and elderly who may need them more than others. Is the FDA pulling older and more affordable opioids off the shelf because they do not have this new technology? Is the cost of medical care and denial of coverage being driven by the 5% of addicts in this country, by expensive prison empires to house them, by headlines and politicians?

Cost is the issue that limits care. When Medicare & PPO coverage is cut for all of us, will the cost of drugs be one of the major reasons? Answer: it already is.

Remember, the FDA does not have a majority of pain specialists on pain-related advisory committees, only 3 out of 11 MD’s sat on the FDA committee that limited use of short acting fentanyl medication for cancer pain. Opioids may be an essential option for some of my patients yet their PPO will not pay for it — it’s restricted to cancer patients. PPO’s will not pay for many nonopioids used for pain either.

Does the FDA think oncologists know more about treating pain than a pain specialist? The answer is definitely no! Oncologists do not, and some abuse their power to prevent pain relief. Research has shown severe untreated pain in 34% of cancer patients among oncology specialists in the Northeastern US, and likely far more in other areas. There are many untold stories about oncologists who do not treat pain or who use poor practice treating pain, even at major cancer centers. Pain is not their priority and most spend no time learning the needed expertise.

So no coverage for PT, for off label medication, for compounded medication, for opioids restricted to cancer pain, for expensive medication, and increasing regulation for older and more affordable opioids if they have not been pulled off the shelf by the FDA.

Cost cuts imposed major losses in pain management. PPO cuts were severe at least as far back as the mid 1980′s. In 1990, UCLA closed its Anesthesiology Interdisciplinary Pain Center, only 15 years after the first international pain society meeting. Laid off with two weeks notice was the President of the American Pain Society and distinguished researchers in the field. Soon after that, in the hallways of the annual pain society meeting, whispered rumors spread that almost all university centers had closed their interdisciplinary pain centers. Only a few remained, but there was silence on the subject from the platforms and leadership and media. UCLA paved over the only therapeutic swimming pool in the greater Los Angeles area in order to build yet another radiology center.

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The Era for Procedures

There has been a rapid increase in interventional procedures with almost all pain specialists shifting to high reimbursement and easily funded techniques, but where’s the science? Read the practice guidelines of the Academy of Neurology and American Pain Society on epidurals and nerve blocks. Where are the studies that show their benefit? Are they suitable as the best choice?

Pain management requires individualized care that involves analysis and specific treatment based upon many factors. Medicare and PPO’s will pay for procedures which are inversely proportional to the time needed for analysis. There is no single evidence based protocol that can be applied to every one such as there is for chest pain.

With so little research funding and so little training going into pain management,  politics may make the treatment of pain subject to more and more irrational or unaffordable choices.

The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

To Find My Home Page, click here:  Welcome to my Weblog on Pain Management!

In special circumstances, I may suggest a trial of low dose oral ketamine. It is formulated by a compounding pharmacist as an oral suspension. It is safe to use without significant adverse effects, though you may experience transient symptoms lasting 20 to 40 minutes after the first few doses. For most people, it may relieve pain when all other methods have failed, possibly including total pain relief with no side effects in patients who have then been able to discontinue all opioids.

Keep all your medicine, opioids and ketamine, in a lock box to prevent abuse by others. This is a Schedule III drug like Vicodin.

Achieving control of chronic pain requires a partnership

based upon trust and effort

Requirements: I will work closely with you on ketamine and ask you to keep a log of pain before each dose and 30 minutes after. In addition, for the first week I ask that you log blood pressure and heart rate before each dose and 30 minutes after. This requires that you see me in the office one week later. If you have any questions or problems, I ask that you call me the same day, whether it be weekend or holiday. If you are unable to keep these logs before and after the dose, and the appointment one week later, the trial will be discontinued. You have no authority to continue without my consent.

Blood Pressure: Usually no change occurs in blood pressure. Some have reported that ketamine lowers their blood pressure and they are lightheaded when they stand up. If your blood pressure drops or if you are lightheaded, be very cautious as that may lead to fainting and brief loss of consciousness. Anytime a person faints, that could result in potentially serious injury such as hip fracture, other fractures, bleeding or brain injury if you strike your head. Your blood pressure should be above 100 when standing.  Ketamine has been reported to increase blood pressure and pulse, but I have not found that to occur with these doses.

Side Effects: Ketamine has a very narrow therapeutic window for pain control. This means that once you find the dose that relieves pain, a very slight increase in dose may produce intolerable side effects. Unfortunately some patients reach a dose that produces side effects before they experience any pain relief.

Most patients have no side effects with the low doses used by this protocol, though some may have mild symptoms lasting up to 40 minutes. If you do, then try decreasing the dose a small amount.

It is possible but rare that you may experience severe, frightening hallucinations or may feel you are outside the body observing it do things, called a dissociative reaction.

These side effects are dose related and have been short lasting, usually no longer than 40 minutes.  The antidote is Ativan.

Steps to follow: Read all steps carefully before you begin

• Take ketamine 30 minutes prior to your other pain medication

• For the first dose, remain seated or lie down for 20 minutes after you take the dose to avoid risk of falling. Do not take the dose and walk around.
• A few persons have had severe imbalance lasting 10 or 20 minutes. This has resolved after the first few doses in those persons. It may not happen to you, so test with caution. If it has not occurred at the first dose, it is unlikely to occur at all.

• Follow the dosing guidelines in the log I give you and which I repeat in this next step:
  Begin with 0.25 mL and increase by increments of 0.25 mL every 6 hours or longer than 6 hours, until you have some pain relief. Do not increase that dose or dosing interval.

Example: begin 0.25 mL, then 0.5, next 0.75, 1.0, 1.25, 1.5, 1.75, 2.0

If you have had no effect on pain by 2.0 mL, schedule an appointment for further instructions.
If your pain decreases only 1 or 2 points, that is your dose.  It will NOT get better by increasing the dose.  Stop increasing.

• If you have intolerable side effects, you may use 1 or 2 Ativan tablets immediately as an antidote, and every 30 minutes, up to 5 of them.

• CAUTION: Be alert to the opioid-sparing effects of ketamine!

This means that if ketamine relieves your pain, you do not need to take the opioid as that would be an opioid overdose and may cause serious side effects.

Reduce or temporarily stop your opioid medication if pain is gone after using ketamine.

This is why you take ketamine 30 minutes before the opioid. Some people have been able to completely stop all opioid medication due to pain relief from ketamine alone.

• CAUTION: Do not drive for 6 hours after a dose.

This is for the protection of you and others. You may not be aware of very subtle side effects.

• You may take a dose every 6 hours, or longer than 6 hours. Less is more.

If ketamine loses its effect, stop use for 2 or 3 days, then resume. It can be a fickle drug.  That is why increasing the dose causes loss of effect.

Some take ketamine only before sleep. If you do that, use it 30 minutes before sleep in order to log its effect and take blood pressure/pulse before and after. Continue this initially until further changes are approved.

Ketamine was approved for use as an anesthetic by the FDA in 1970

It’s use for pain is “off label” as it was approved only in high doses for anesthesia. It has been used safely in babies. Unlike opioids, it does not depress breathing or bowel function, and usually does not depress cardiovascular function. Since the late 1980′s, numerous scientific articles have been published on its use as a third line choice for some pain conditions; there are few double blind control studies, one is listed below. If you search ketamine on various internet search engines you find it is abused by addicts just as other drugs are. You find medical articles when you search the literature using  Google Scholar or PubMed in the National Library of Medicine. If you find a medical article with adverse effects, let me know. I have spoken to leading brain and psychiatric researchers who have verified there are no lasting side effects from its use.

Many publications on ketamine use multi-day infusions at much higher dosages than the oral dosages in my protocol. Drexel University has treated over 3,000 patients with infusions of 40 mg/hour for 5 days with no lasting adverse effects. Even higher doses than that are used for surgical anesthesia. Ketamine is a powerful tool for treating pain.

Medical Publications

You can click and download each reference in blue below

High dose ketamine improves neurological outcome after stroke in rats, Reeker et al, Canadian J Anesth 47:572-578, 2000

Ketamine, Pasero C, McCaffery M, Amer J Nursing, 105:60-64, 2005
An excellent review, more clinical, easier to read than some more technical papers

Ketamine in Chronic Pain Management: An Evidence Based Review, Hocking & Cousins, Anesth Analg, 97(6):1730-1739, 2003 This nine page article is the best comprehensive review of ketamine’s use in almost every known pain condition including post stroke pain.  Easier to read; a catalogue of pain syndromes and references.

Ketamine Stops Aura in Familial Hemiplegic Migraine, Neurology, 55:139-141, 2000 Two mechanisms may account for this. First, ketamine can increase cerebral blood flow, which may counteract the marked hypoperfusion induced by cortical spreading depression, as observed in migraine with aura. Second, in experimental animals, ketamine accelerates the  restitution of neuronal function after hypoxia.

Ketamine oral use in 8 chronic pain patients, Canadian J. of Anesthesia, 2004

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The Reflex Sympathetic Dystrophy Association library has many articles on RSD, CRPS and ketamine. Remember most of the articles are written for scientists and physicians.

From their library I particularly recommend the first article, below.  The last two are very technical but important new research.

Expectations of Pain: I Think, Therefore I Am, Jones-London M, National Institute of Neurological Disorders and Stroke

For pain mechanisms, read
Beyond Neurons: Evidence that Immune and Glial Cells Contribute to Pathological Pain States, Watkins L and Maier SF, Physiology Review. 2003;82:981-1011.

For pain mechanisms, read
Complex Regional Pain Syndrome (CRPS): Evidence of focal small-fiber axonal degeneration in complex regional pain syndrome-I (reflex sympathetic dystrophy),  Oaklander AL et al., Pain. 2006;120:235-243.

There is no link to the following double blind controlled research publication:

Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous Ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage 2000;20:246-252. Mercadante et al compared intravenous infusions of Ketamine (0.25 and 0.5 mg/kg) with placebo in a double-blind, crossover study of 10 cancer patients with neuropathic pain.

Please note that the free Adobe Acrobat Reader is needed to read some references.

You can download the free reader now.

~~~~~The material on this site is for informational purposes only, and is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider. ~~~~~

Low Dose Naltrexone

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Low dose naltrexone, or LDN, has been prescribed “off label” for persons with many conditions including intractable pain, chronic fatigue syndrome, complex regional pain syndrome, RSD, Multiple Sclerosis, Parkinsons Disease, IBS, inflammatory bowel disease, autoimmune diseases and Crohn’s Disease to mention only a few. Low dose naltrexone is not a cure but may be potentially helpful for selected persons with these conditions. It appears to have little or no toxicity at this low dose – a few persons report transient insomnia, nausea or vivid dreams.

Naltrexone and and naloxone are both classified as morphinans, meaning morphine-like. The action of the morphinans and dextromethorphan is on the glia. This discussion relates to those medications. Refer to the paper titled Morphinan Neuroprotection by Zhang, below.

How does it work?

Naltrexone and dextromethorphan are anti-inflammatory. They act centrally and are very different from, and without the toxicity of commonly used anti-inflammatory medications such as ibuprofen or steroids.

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They inhibit Superoxide, a free radical, and reduce the toxicity of peroxynitrate metabolism and the excitotoxic effects of glutamate. The mechanism of action occurs at the microglia in spinal cord and brain where they are neuroprotective. Microglia are the immune cells of the central nervous system. Microglia are not only the hallmark of pathology in Multiple Sclerosis but they also play a major role in pain and other degenerative neurological conditions. Reducing the damaging effect of these potent neurotoxins improves function of the immune system and various organ tissues including the spinal cord and brain.

There is evidence that they also increase the release of neurotrophic factors BDNF and GDNF (Jau-Shyong Hong, PhD, at the NIEH/NIH, personal communication).

Chronic pain alters central processing by changing the neurochemistry and the anatomy. This can lead to premature aging of the brain with loss of gray matter and brain atrophy as reported on MRI’s of persons with chronic low back pain. This may also occur in other stress-related disorders, such as chronic depression or post-traumatic stress disorder.

There has been a blossoming of basic neuroscience research on microglia that began in the 1980′s. At the American Pain Society meetings in San Diego in May 2009, there were hours of lectures for several days on the basic science of microglia and pain mechanisms.  This confirms the experience that I have seen clinically.

I am grateful to have the guidance of patients, physicians, and scientists in learning about the use and mechanisms of low dose naltrexone, with special thanks to Dr. Jau-Shyong Hong, PhD, Chief of Neuropharmacology at NIEH/NIH. He is one of the country’s leading experts on microglia, opioid antagonists and morphinans and has published some of the references below.

New science shows naltrexone to be a potent anti-inflammatory — much stronger and with a much different mechanism than the weaker cox inhibitors such as ibuprofen, Vioxx, Celebrex, Naproxen with none of those adverse side effects. Dr. Hong reports that in animal studies, dextromethorphan is even stronger than naltrexone.

Naltrexone is one of a few compounds called morphinans, meaning it has a structure similar to morphine, but naltrexone blocks morphine-like medication:  it is an antagonist.  For detailed discussion of morphinans refer to the article by Zhang et al, listed below.

There are links to further understand the basic science in medical publications and references below. We all owe thanks to patients whose clinical recovery with the use of low dose naltrexone has kept this work alive since its effect on the immune system in Multiple Sclerosis and HIV/AIDS was discovered by Bernard Bihari, MD, in 1984. He was a Harvard trained academic neurologist based in NYC. Their testimony can be found in the book mentioned below or in many web sources. The excitement of their recovery and their fundraising prompted UCSF and Stanford to begin double blind studies now 25 years later.

Recent clinical research

In 2009, Drs. Younger and Mackey of Stanford Pain Center reported a double blind study of low dose naltrexone in persons who had fibromyalgia more than 10 years and showed 30% improvement in pain and fatigue. They now plan a larger study. Bruce Cree, MD, of the UCSF Multiple Sclerosis Clinic in 2008 reported improvement using low dose naltrexone in a masked placebo controlled study to evaluate quality of life in MS [reference below] testing only pain, cognitive function and mental health. They propose doing a larger study to measure other functions in MS. In the 2007 study by Jill Smith, MD, at Hershey Medical Center [reference below], 67% of persons with Crohn’s Disease achieved remission in a few weeks, and total 89% had a response to therapy. As described in their publication: “Endogenous opioids and opioid antagonists have been shown to play a role in healing and repair of tissues.” Dr. Smith has received a $500,000 grant from NIH to continue research on low dose naltrexone for Crohn’s Disease.

Multicenter studies on LDN for persons with Multiple Sclerosis have been done in Italy and Scotland.  New research is starting in Scotland that will include study of the toxicity of peroxynitrate metabolism in MS first proposed by a Nobel winning scientist in 1991, see the reference on peroxynitrate metabolism and Dr. Gilhooly’s references, below.  Scotland has the highest incidence of MS in the world, even higher than Great Britain and Ireland.  Dr. Gilhooly’s patients reported remarkable improvement in function on LDN that led to him starting this work.

My experience prescribing LDN

I have been prescribing naltrexone for 6 years in ultra-low microgram doses, and more recently prescribing low dose naltrexone at doses of 1 to 4.5 mg.  It is one of the most exciting developments in pain medicine and neurodegenerative diseases that I have ever seen.  It was previously unimaginable to me to see some persons with intractable pain now pain free and off opioids because of low dose naltrexone or a similar medication that will soon be posted on this weblog.

I have not yet been able to predict who will respond to low dose naltrexone with decrease in symptoms, but many patients have had profound relief. Often it may reduce intractable pain to zero despite failing to respond for many years to all known therapies. Inability to predict a response to pain is true of many classes of medication that we trial “off label” for pain relief and even those that are FDA approved for pain. Paradoxically, the same is true for morphine and similar strong opioids.  In fact, opioids relieve pain and opioids create pain at the same time, and it is not uncommon for pain specialists to see individuals with severe pain despite using high dose opioids.

“Off label” use means it is not FDA approved for these purposes.  Instead, low dose naltrexone is used in small doses of 1 to 4.5 mg at bedtime that must be made by a compounding pharmacist, rather than the 50 mg tablets or higher doses that are FDA approved for prevention of addiction and alcoholism.

Many thanks to the sponsors and speakers of the Fourth Annual Conference on Low Dose Naltrexone which was held for the first time on the West Coast at USC on October 8, 2008 – they have provided other references attached below.

Naltrexone became available as a generic drug many years after 1984, and thus there is no profit in this use for pharmaceutical companies.  Only recently, has the science progressed enough to understand its new uses.  Therefore what you may read in various sources on the web may be the “old science,” whereas the articles below are the “new science.”

I will be updating this page in the near future but wanted to make these recent publications and documents available now.

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Update June 22, 2010: Check back for patient case reports I will be publishing soon now that I have more specific information on how morphinans work on path pathways and on the central nervous system.

I recommend this book:

The Promise of Low Dose Naltrexone Therapy

by Elaine A. Moore & Samantha Wilkinson, McFarland & Company Inc., 2009

“Grounded in clinical and scientific research, this book describes the history of naltrexone, its potential therapeutic uses, its effects on the immune system, its pharmacological properties, and how the drug is administered. It also lists … patient resources, and includes interviews with LDN patients and researchers.”

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If you are unable to view and print PDF files below,

download the free PDF reader.

If you do not have Microsoft Powerpoint software to view slides,

download the free Microsoft Powerpoint Viewer .

Download sizes are in parentheses to the right of each download link.

·

Morphinan Neuroprotection by Zhang, Hong, Kim, et al, Crit.Rev.Neurobiol. 16(4):271-302, 2004 (PDF)  450k

Microglia Mediated Neurotoxicity Molecular Mechanisms. Block Zecca Hong, Nature Reviews Neurosci 8:57, 2007 (PDF) 529k

Peroxynitrites in MS,  Dr Tom Gilhooly, Scotland, USC 4th Annual LDN Conference 2008 (PDF)  77k

LDN research on MS in Scotland Dr Tom Gilhooly, USC 4th Annual LDN Conference, 2008 (Powerpoint)  12M

LDN In MS, Bruce Cree MD, UCSF Poster, 2008 (PDF)  154k

A Pilot Trial of LDN in Primary Progressive MS, Gironi et al, Multiple Sclerosis 14:1076–1083, 2008 (PDF)  222k

LDN for Treatment of MS – Clinical Trials Are Needed, Patel, Ann Pharmacotherapy 41 (9):1549, 2007 (PDF)  114k

LDN Improves Active Crohns Disease, Jill Smith MD et al, Am J Gastroenterology 2007 (PDF) 121k

LDN Immune System Autism & HIV, Vojdani, USC 4th Annual LDN Conference, 2008 (Powerpoint)  5.7M

LDN Immune System Autism & HIV, Vojdani Part 2, USC 4th Annual Conference, 2008 (Powerpoint)  3.6M

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Update December 10, 2010:  For further research publications on glia, please refer here.

Refer here for a case report of severe RSD responding primarily to naltrexone.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

Posted in Chronic Fatigue, Complex Regional Pain Syndrome, Crohn's Disease, CRPS, Dextromethorphan, Fibromyalgia, Low Dose Naltrexone LDN, Naltrexone, RSD Tagged: Chronic Fatigue, Crohn's Disease, CRPS, Dextromethorphan, Fibromyalgia, LDN, Low Dose Naltrexone, Multiple Sclerosis, Naltrexone, Pain, Parkinson's Disease, RSD ]]> http://painsandiego.com/2009/05/26/low-dose-naltrexone-ldn/feed/ 5 painsandiego Lavender sprig The Promise of Low Dose Naltrexone Therapy Lavender field http://painsandiego.com/2009/04/25/mayo-clinic-health-manager-a-free-tool-to-manage-your-familys-health-online/ http://painsandiego.com/2009/04/25/mayo-clinic-health-manager-a-free-tool-to-manage-your-familys-health-online/#comments Sat, 25 Apr 2009 20:57:31 +0000 Nancy Sajben MD http://painsandiego.wordpress.com/?p=672 ]]>

The Mayo Clinic has announced a Health Manager, hosted and powered by Microsoft Healthvault, to help you manage your own and your family’s health and medications.  It is a “security enhanced” online interactive personal guidance system that allows you to track and graphically monitor specific problems, and access Mayo Clinic advice about diagnoses and treatments.

You can enter your physician’s names and telephone numbers, organize immunizations, charts, chemistry studies, and tests then customize and print relevant information to take to your doctors.  In coming months, persons with Type 2 diabetes, hypertension or high cholesterol will find help managing those conditions, and the site will be updated regularly to reflect best practices in health care.

This allows you to become more pro-active in your care, print out material to take with you to your doctor, and get the most out of your doctor’s visits.

Warnings about electronic health records:  Inaccuracies can have serious consequences and a list of medical conditions should have starting and ending dates on them, as this article points out. ”For example, … an inaccurate diagnosis of gastrointestinal bleeding on a heart attack patient’s personal health record could stop an emergency room doctor from administering a life-saving drug.” If a doctor knew that was 20 years ago, not 2 years ago, that may be a mortal difference.

Yes, you type that in.  Be careful.  One small zero, one typographical error, one person’s life.

I would raise a word of caution that no personal information is that safe on the web. Even top secret military websites have been hacked.  Consider using code names, or at the least make certain that no medical record numbers are on any of those reports.  Use long passwords and change them often.   That would help.  Medical Identity Theft is a very real issue that may never be untangled if it were to occur.

Here’s more on that from today’s Wall Street Journal; note comments below the article:  Are Electronic Health Records Worth the Risks?

Risks for Patients —Liability for Doctors:

More importantly, this excellent article by Dana Blankenhorn in ZDNet Healthcare points out the 2008 Riegel vs. Medtronic decision … gave tech companies immunity from most state lawsuits, if their software is placed into a device.

….The Journal of the American Medical Association, which has its own problems with criticism, has now published an editorial decrying the immunity, which is based on a doctrine called “learned intermediaries.”  Present law assumes that faults lie with the user, writes Ross Koppel … a sociologist at the University of Pennsylvania. “Health IT vendors claim that, because they cannot practice medicine, clinicians should be accountable for identifying errors resulting from faulty software or hardware,” he said in a press release.

~~~“But errors or lack of clarity in HIT software can create serious, even deadly, risks to patients that clinicians cannot foresee.”~~~

In his article, Koppel and David Kreda, a Philadelphia software designer, offer examples of software bugs causing mistakes in drug administration, and failures to carry over warnings about drug allergies to the clinicians using them.

All this hit like a thunderclap for Scot Silverstein of Drexel, the health IT skeptic profiled here last month, who blogs at Healthcare Renewal under the nom de blog MedinformaticsMD.

~~~ Along with your patients you are nonconsented beta testers and experimental subjects

of the health IT industry,

and potential victims of the computer industry’s arrogance and dysfunction.~~~

Silverstein believes that legal threats are necessary to end the “mission hostile user experience” he finds so often.

Dr. Koppel writes “Even when their products are implicated in harm to patients, manufacturers of healthcare information technology (HIT) currently enjoy wide contractual and legal protection that renders them virtually “liability-free.”  His work on the benefits and the liabilities of HIT has been the subject of international focus.

In one example, a trauma team did manage to catch an error in a piece of faulty vendor software that miscalculated intracranial pressures. Had they not, patients would have been severely threatened and the hospital would have been responsible for the resulting harm. “From an equity standpoint,” says Dr. Ross Koppel, “This is unacceptable.”

Other examples of internal software mistakes include confusing kilograms and pounds used to derive medication doses based on a patient’s weight, and software that erroneously remove warnings about fatal drug allergies. In both cases “learned intermediary” clauses hold that clinicians are responsible for noticing the mistake before prescribing.

Equally unfortunate and unacceptable are the provisions in most HIT contracts that prohibit healthcare organizations from openly disclosing any problems caused by vendor software, even to the other HIT licensees using the same products, e.g., clinicians, hospitals. Such stipulations defeat patient safety efforts and are contrary to the principles of evidence- based medicine, says Koppel.

The authors also identify circumstances where HIT vendors should not be held accountable for patient safety failures arising from their products’ misbehavior, e.g., user misuse and medical circumstances not knowable in advance. “Legal and contractual changes must not reduce incentives to vendor innovation,” said Koppel. “We must achieve a better balance among patient safety concerns, fairness to clinicians, vendor responsiveness, and vendor marketing.” The authors suggest moving the HIT industry toward this balance may require several changes to the status quo, including:

• State and national organizations with responsibility for inspecting hospitals would have additional power to set rules affecting HIT contract terms.
• Professional medical organizations taking a stand that HIT contracts containing blanket “hold harmless/learned intermediary” clauses are inconsistent with professional practice. Vendors would then have to focus more strongly on patient safety concerns.
• Healthcare professionals and their associations lobbying Congress for changes in federal law that would recognize a range of HIT vendors’ safety responsibilities–much as with auto manufacturers and seatbelt laws.
• Altering legal standards to facilitate rather than frustrate disclosure of HIT product shortcomings that have patient safety implications.

The American Recovery and Reinvestment Act of 2009 (ARRA) – What it means for doctors

The New England Journal of Medicine this month published a detailed article on Health Information Technology [HIT] pointing out the “significant barriers to their adoption and use: their substantial cost, the perceived lack of financial return from investing in them, the technical and logistic challenges involved in installing, maintaining, and updating them, and consumers’ and physicians’ concerns about the privacy and security of electronic health information.”

Experts estimate the cost of a system for a medical office to be about $40,000 — startling indeed.  That may explain why so few have invested.  And there will be sticks and carrots to get this going. Starting in 2011, doctors will receive financial incentives from Medicare for the “meaningful use”  of a “certified” system “that can exchange data with other parts of the health care system.”  And if they do not have a system, reimbursement from Medicare and Medicaid will be reduced.  Obviously this does not apply to private insurance, nor does it apply to the growing numbers of doctors who opt out of Medicare because of low reimbursements that are not adequate to cover overhead.

To get the most out of the fiscal incentive, an MD must have the system fully operational by 2011. The incentives are reduced every year until they end in 2016.

The law currently requires health care organizations to promptly notify patients when personal health data have been compromised.  But should tech companies be given immunity from lawsuits if their software causes problems in your health or if data is not secured, resulting in Medical Identity Theft?

Enjoy this music:  Louis Armstrong  and don’t miss the video.  It’s magical.

What a Wonderful World

The bright blessed day, the dark sacred night.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!