Spinal Cord Stimulators – comment on RSD


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Spinal Cord Stimulators 

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 Craig’s comment

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By no means do I mean to say that I or anyone else has better insight into how to treat pain, but I am against spinal cord stimulators [SCS’s] for treatment of pain due to CRPS, and possibly against use in other situations. I demand that the billions in profit they made be put into a retrospective and prospective study of damage caused by them in order for them to give full informed consent.

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I have 3 goals writing this.

  1. SCS’s

  2. Craig’s experience

  3. The Only Real Answer for severe pain, not damaging the system with opioids

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Informed consent is never given for spinal cord stimulators because it requires truth telling, something our corporations have been reluctant to do. Business ethics are not medical ethics, as we keep being reminded daily in the headlines.

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I enclose, below, a generously expressed and detailed comment by a man who had the patience to sit down and  write the painfully gory details so you can weigh-in on your decision whether to follow your pain specialist’s opinion to give you one. I don’t want anyone to feel suckered into choosing them and if I had pain I’ll admit I’d crave relief too. Anything. I’d be in line before the doors open.

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But if you have CRPS, spinal cord stimulators will create more pain. CRPS evolves unpredictably, by a will of its own. I know some very desperate patients with CRPS everywhere including face, mouth, gums, tongue, organs, trunk, limbs. Spinal cord stimulators will create more pain. Keep in mind, I don’t see the 5 year success stories even for lumbar disc pain. They don’t need me if they are pain free.

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But if you have CRPS and desperate need for pain relief because all else has failed — every known drug in highest possible doses of ketamine, propofol, opioids for weeks in ICU fail to even touch pain— there is one thing, and only one thing to do and I will set it out below. I just sent my recommendation to a patient with CRPS in extreme pain.

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My recommendation, below, is for patients who have nowhere else to turn.

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First I’ll mention the problems Craig encountered with SCS’s. He sent his comment to the opening page of this blog, so I will reproduce below. 

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I am currently undergoing a trial Medtronic SCS. I have had to have it reprogrammed 3 times since it was installed 5 days ago. I have had sensations and issues that I have addressed with my rep and my neurosurgeon. I get a severe headache when the unit is turned on. I get the constant feeling of having to urinate. I have current running through my testicles which they can not seem to program out and I am getting little pain relief. I have had to failed back surgeries, many failed injections and I have CRPS. The leads that were inserted when I was in the table covered my mid back and both legs. After I got to my feet and waited while they programmed the unit in another room. They came in and plugged it in and I no longer had coverage on the right side. My crps is in both legs, my hands, arms and face. The lyrica helped to tamp down some of the burning but I am in pain 24/7 and this was my last resort. I have scar tissue completely surrounding my S1 nerve. By the grace of God, I am on my feet, on crutches. I seem to get a look of disbelief when I tell them the unit is causing these issues or it’s not giving me the relief I was counting on. Relief, only to cause greater issues and pain. Is not relief to me. I can not wait to get this trial out of my back. I believe the leads slipped and that is why I am not getting the full coverage I had on the table. The issues I have had are as follows: severe headache, constant feeling of having to urinate, extreme joint pain, abdominal pain, sleeplessness, involuntary jerking, surges in current even when sitting still. Intense pain around the lead insertion site. Current uncomfortably running through my testicles, regardless of setting. It is my opinion there is still not a lot known about crps and I have read evidence of people have great success with these units. Everyone reacts differently. My body obviously creates a lot of scar tissue and my orthopedic surgeon created a fair amount herself. I can’t imagine even more or being forced into a chair for yet another unlucky decision. The medication helps and I have lived this far without the optimism that it would end soon. I had high hoed for this device but I don’t think it is right for me.

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One of my patients with CRPS was hospitalized for weeks with recurring unusual abscesses and required repeated surgery of hand and forearm. Even before surgery, she had failed opioids, failed ketamine, and was in ICU for weeks and weeks while the same medications were still given along with Propofol and IV Tylenol. Nothing helps her extreme pain.

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Anesthesiologists on staff in ICU threw everything they had at the pain for weeks. Most anesthesia pain doctors would have probably done what they did because that is the limit of tools we have.

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When you have hit the limit of benefit from opioids, ketamine, propofol, we have nothing else that treats pain with one exception: drug holiday.

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Stop all analgesics including Tylenol that destroys the liver as severely as cancer, the severity of which was newly discovered and published yesterday.

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The receptors for these analgesic drugs have up-regulated to such an extent they have caused the situation. Again, I stress, everything that was done during the ICU admissions would be done by any anesthesiology pain specialist. Those are the only tools. They cause the problem. The same for opioid induced hyperalgesia. We used to do it with Parkinson’s drugs in the 80’s.

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The only way to rehabilitate the up-regulation of all those receptors that have now exploded in numbers, immune to anything you throw at them, is stop the drugs.  Stop all of them for weeks, maybe months, years, no one knows, you are all the human guinea pig waiting to happen. But if we restart them, how long do we wait, how quickly will it again lead to this massive hyper-excitable state of pro-inflammatory cytokines that we know have gone wild, flooding the CNS. A flooded engine will not restart.

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Ketamine at least is known to reduce pro-inflammatory cytokines, but the system is too busy exploding, birthing new receptors that take over, and you’ve got a 55 car pile up. Well, more like millions I’d guess. No scientist here. Clnically, when can we resume something after a drug holiday, how soon and which drug? I’d avoid opioids because they create more pro-inflammatory cytokines. Choose ketamine, because they reduce pro-inflammatory cytokines, but if it works at all, stop it at first sign of tolerance, which is the need for increased dose. It becomes less effective. Walk a fine line, endure more pain because unless you do, it will no longer help. Opioids, analgesics of many kinds. 

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How do we get you through a drug holiday because we know withdrawing these drugs will trigger even more pain for possibly weeks until the system settles down?

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Pain storms, hurricanes

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This is complex regional pain syndrome where we see this insanity of pain storms. There is no other condition, unless several neuropathic pains in people with cancer, nowhere I have seen this type of pain in decades except CRPS – comparable to pain of subarrachnoid hemorrhage, blinding pain.

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No one has answers. None. One university does outpatient infusions of ketamine six hours daily for 8 to 12 weeks. Does it help? A small percentage. Outpatient, 6 hours daily, 5 days a week, staying at a hotel, 8 weeks.

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This is CRPS/RSD. No one has answers. It is futile to throw more of the drug in the system. That is my opinion. You have a choice and may choose otherwise. It is your body. You may stay on monthly opioids for decades, until you finally admit how poorly they work. A drug holiday is what we did in the 70s during my ancient training with Parkinson’s patients. They needed full 24-hour support. The American medical system has changed since then and those are not options currently available—cost.

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You need full psychological and psychiatric support.

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The Only Real Answer

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The country needs to invest $10 million to complete the clinical trials needed for an injectable, long-lasting interleukin 10 [IL-10], the anti-inflammatory cytokine. It already has full scientific and animal studies performed by and with the world’s foremost glial scientist at University of Colorado Boulder. Professor Linda Watkins has won awards from many countries. She has been the keynote speaker at the annual academy pain meetings for years. IL-10 can relieve pain for three months in animals that have intractable chronic neuropathic pain. This is not new —–NIH I’m looking at you to fund clinical trials. And those of you who care, do a Kickstarter to fund the clinical trials.

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This is the power of the innate immune system. NIH would rather fund research on the unknowns like stem cells rather than the known. It’s known for decades, NIH does not like to fund pain research. Glia are not all about pain. They are the innate immune system, the key to Alzheimer’s, neurodegenerative diseases, almost all known disease including atherosclerosis. It’s all about inflammation. We need the trials to stop giving drugs that cause inflammation, opioids —–CDC fiats are not as good as a drug that relieves pain, a drug that really works on mechanism. Where will the addicts go if the ER only has IL-10 for pain? That is one way to overspend on ER visits.  And NIH, please get us some real clinical research funding on how to use glia for our benefit. Get us some research on the entourage effect, combining medications to achieve relief especially for neuropathic pain.

Then bring on some crack negotiating teams from insurers to do some negotiation about pharmaceutical prices. Our new president has mentioned that.

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Please bring this to everyone’s attention. One way to get a grip on pain and/or depression is to build hope, help others, and energize behind a goal.

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Kickstarters work to raise tens of millions overnight. 

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IL-10 – animals have been shown to be pain free for three months, already proven in animal studies, by one of the world’s most widely acknowledged pain specialists Professor Linda Watkins, PhD. We need the final steps to fund the clinical trials in humans.

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The material on this site is for informational purposes only.
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It is not legal for me to provide medical advice without an examination.

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

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If you wish an appointment, please telephone the office to schedule.

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

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Treatment for Pain Could Last Months: Botox & Tetanus Chimera Injection


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Professor Bazbek Davletov now at Sheffield University, UK, reports his research that is featured on the cover of the October 2013 journal Bioconjugate Chemistry. He hopes the drug will cost around £1,000 a year, making it cheap enough for use on the NHS. It is authored by a 22-person team from 11 research institutes, including Lincoln University UK based Dr Enrico Ferrari.

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Dr Ferrari joined the School of Life Sciences in October last year from the Medical Research Council’s Laboratory of Molecular Biology in Cambridge, where he took part in the development of a new way of joining and rebuilding molecules in the research group of Professor Bazbek Davletov who was then at the MRC.

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Taking components of clostridium botulinum and clostridium tetani neurotoxins – known as Botox and tetanus toxin – they re-joined the molecule proteins using a ‘protein stapling’ technology targeting central neurons without unwanted toxic effects.

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Science Daily announcement:

‘Chimera’ Protein Could Lead to Drug Treatments for Chronic Pain

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Lincoln University, UK, heralds this promising discovery:

Scientists synthesise new ‘chimera’ protein which could herald future drug treatments for chronic pain

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“Scientists have manufactured a new bio-therapeutic molecule that could be used to treat neurological disorders such as chronic pain and epilepsy.”

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The molecule was able to alleviate hypersensitivity to inflammatory pain.

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“Dr Ferrari, who is one of the lead authors of the study, said: “The toxins were split into parts so they were unable to function. Then later they were reassembled using a ‘zipping’ system so they can operate in a safe way. The re-engineered chimera toxin has very similar characteristics to Botox and is still able to block neurotransmission release, but the paralytic effect is a lot less. We then added a tetanus molecule which targets the chimera to where the pain signals travel towards the central nervous system.””

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“Dr Ferrari added: “Many painkillers relieve the pain temporarily and have various side effects. The selling point of this molecule is that the pain relief could last up to seven months….””

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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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Please understand that it is not legal for me

to give medical advice without a consultation.

If you wish an appointment, please telephone my office.

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

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Opiates Create Pain – A New Pathway Mediated by Microglia


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Though morphine and other opiates are the gold standard for producing analgesia, paradoxically they may create pain.

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The mechanism, a microglia-to-neuron pathway in the spinal cord, has now been discovered by Ferrini et al. It was published in the on-line edition of Nature Neuroscience

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“Morphine hyperalgesia gated through microglia-mediated

disruption of neuronal Cl homeostasis.”

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Their research was reviewed January 8 in Medical News Today, exerpted below:

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….”Our research identifies a molecular pathway by which morphine can increase pain, and suggests potential new ways to make morphine effective for more patients,” says senior author Dr. Yves De Koninck, Professor at Université Laval in Quebec City. The team included researchers from The Hospital for Sick Children (SickKids) in Toronto, the Institut universitaire en santé mentale de Québec, the US and Italy.

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New pathway in pain management

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The research not only identifies a target pathway to suppress morphine-induced pain but teases apart the pain hypersensitivity caused by morphine from tolerance to morphine, two phenomena previously considered to be caused by the same mechanisms.

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“When morphine doesn’t reduce pain adequately the tendency is to increase the dosage. If a higher dosage produces pain relief, this is the classic picture of morphine tolerance, which is very well known. But sometimes increasing the morphine can, paradoxically, makes the pain worse,” explains co-author Dr. Michael Salter. Dr. Salter is Senior Scientist and Head of Neurosciences & Mental Health at SickKids, Professor of Physiology at University of Toronto, and Canada Research Chair in Neuroplasticity and Pain.

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“Pain experts have thought tolerance and hypersensitivity (or hyperalgesia) are simply different reflections of the same response,” says Dr. De Koninck, “but we discovered that cellular and signalling processes for morphine tolerance are very different from those of morphine-induced pain.”

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Dr. Salter adds, “We identified specialized cells – known as microglia – in the spinal cord as the culprit behind morphine-induced pain hypersensitivity. When morphine acts on certain receptors in microglia, it triggers the cascade of events that ultimately increase, rather than decrease, activity of the pain-transmitting nerve cells.”

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The researchers also identified the molecule responsible for this side effect of morphine. “It’s a protein called KCC2, which regulates the transport of chloride ions and the proper control of sensory signals to the brain,” explains Dr. De Koninck. “Morphine inhibits the activity of this protein, causing abnormal pain perception. By restoring normal KCC2 activity we could potentially prevent pain hypersensitivity.” Dr. De Koninck and researchers at Université Laval are testing new molecules capable of preserving KCC2 functions and thus preventing hyperalgesia.

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The KCC2 pathway appears to apply to short-term as well as to long-term morphine administration, says Dr. De Koninck. “Thus, we have the foundation for new strategies to improve the treatment of post-operative as well as chronic pain.”

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Dr. Salter adds, “Our discovery could have a major impact on individuals with various types of intractable pain, such as that associated with cancer or nerve damage, who have stopped morphine or other opiate medications because of pain hypersensitivity.”

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Cost of pain

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Pain has been labelled the silent health crisis, afflicting tens of millions of people worldwide. Pain has a profound negative effect on the quality of human life. Pain affects nearly all aspects of human existence, with untreated or under-treated pain being the most common cause of disability. The Canadian Pain Society estimates that chronic pain affects at least one in five Canadians and costs Canada $55-60 billion per year, including health care expenses and lost productivity.

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“People with incapacitating pain may be left with no alternatives when our most powerful medications intensify their suffering,” says Dr. De Koninck, who is also Director of Cellular and Molecular Neuroscience at Institut universitaire en santé mentale de Québec.

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Dr. Salter adds, “Pain interferes with many aspects of an individual’s life. Too often, patients with chronic pain feel abandoned and stigmatized. Among the many burdens on individuals and their families, chronic pain is linked to increased risk of suicide. The burden of chronic pain affects children and teens as well as adults.” These risks affect individuals with many types of pain, ranging from migraine and carpel-tunnel syndrome to cancer, AIDS, diabetes, traumatic injuries, Parkinson’s disease and dozens of other conditions.”

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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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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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

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RSD/CRPS, Multiple Sclerosis, LDN & Ketamine


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It is rare for me to see a patient who is not complex.

They have failed so many treatments for so many years before they call.

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This is the report of a lovely woman in her early 70’s with progressive Multiple Sclerosis for 30 years and paraplegia that has forced her to use an electric scooter the last 5 years, and power wheelchair the last 2o years. Because of total paralysis of the right lower limb, she fell and shattered her femur, the thigh bone, in August 2009. Tragically, and all too often, the surgeon failed to diagnose Complex Regional Pain Syndrome [CRPS], even failed to visit her in the hospital. CRPS increased the fatigue she had already had from Multiple Sclerosis.

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Thankfully a physical therapist suggested the diagnosis.

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Why is pain management not a required subject for physicians?

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I have written elsewhere that the American Pain Society discovered that our National Institute of Health, NIH, devotes less than half of 1% of their research dollar to pain research. Of 28 NIH institutes, none for pain, three for addiction. This will not change soon. The only hope is that RSDSA.org will succeed in collaborating with all pain organizations, groups with dystonia, chronic fatigue in order to give a voice and research dollar to advances.

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Before seeing me in September, she had 11 sympathetic blocks with no benefit.

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Does it make you wonder why 11 were done?

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How does insurance authorize 11 when 10 had no benefit? I have just learned that a doctor must indicate at least 50% relief before another will be authorized. That explains it.

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Then she was given opioids including tramadal and Butrans patch which rendered her a “zombie,” sedated, poor memory, unable to function. She tried 4 or 5 treatments of Calmare with no benefit but was advised she needed a clear neural pathway for it to work. That was not possible due to the Multiple Sclerosis.
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Lyrica caused severe edema. Gabapentin 1400 mg/day caused weight gain, increased her appetite  more than usual, but she remained on it. She craves sweets more than usual, at times uncontrollably. Perhaps it can be slowly tapered now. Advil 600 mg gave some benefit but caused ulcers that required Nexium.

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Since her initial visit a few weeks ago, she became 60% better during her two week stay.

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I will highlight only two of the new medications started.

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It may also be said that opioids are not the answer.

Opioids may perpetuate pain.
They may produce paradoxical pain or opioid induced hyperalgesia or windup.

They may block the effect of ketamine and other adjuvants that would otherwise lower pain.

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Of importance is that she was not able to tolerate clothing on her right lower limb for three years, not even a sheet, and now she is able to sleep through the night without pain for the first time in three years and able to wear a skirt. This allows her to go out with family to restaurants and even to enjoy shopping with her daughter. Her dose of ketamine is very small relative to most of my patients and she uses it only once or twice a day since most of the new medications have brought her pain down.

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At her first visit one month ago, she rated pain from 6 to 8 on a scale of 10, average 7/10. Now 60% better, ranging from zero to 7, average 4. Yes zero pain, sleeping through the night without pain and waking without pain. She had not been able to tolerate touch to the right thigh or foot and would pull her skirt above the thigh, removing her shoe.

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Now she indicates pain continues to improve.

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Of interest, despite an abundance of concern that low dose naltrexone [LDN] may flare her Multiple Sclerosis, we were easily able to increase the dose to triple what is usually called “LDN.” This did not flare her condition and may be one of the most effective medications she is taking for pain.

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What is LDN?

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The FDA has sanctioned its use in the USA only in doses of 50 to 400 mg for addiction to opioids and alcohol.

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Low dose naltrexone [LDN] is a fascinating medication. It has been used in low dose in persons with Multiple Sclerosis since 1985 when a Harvard trained neurologist in New York City, Dr. Bihari, first discovered that it relieved all disability in some patients with Multiple Sclerosis and prevented recurrent attacks. Since then, doctors in Scotland, where they have the highest incidence of Multiple Sclerosis, find that one of the earliest signs of recovery in this population is relief of neurogenic bladder. It is said that persons with Multiple Sclerosis must remain on LDN for 1.5 years before they might fully assess its value.

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 Multiple Sclerosis may be flared unless very small doses of LDN are used.

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Many with Mulitple Sclerosis cannot tolerate more than 2 or 3 mg, perhaps due to spasticity. There is a great deal of dogma on the web about its mechanism, dosing and timing for off label use. Use the search function on this site to review the prior discussions I posted on LDN, MS, CRPS.

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Naltrexone is a glial modulator.

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What’s that?!

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By serendipity, four years ago I discovered naltrexone in low dose may relieve chronic intractable pain. I had been using it for perhaps eight years in microgram doses but I found in milligram doses it is even more profound.

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The mechanism of naltrexone and a wee bit of glial research is discussed here. The Nobel Prize was awarded last year for the discovery that these glia are your innate immune system. They are profoundly important in many diseases including chronic pain, Major Depression, Multiple Sclerosis, Alzheimers, Parkinsons Disease, ALS, Autism. They produce inflammatory cytokines that lead to inflammation.

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Now that she has been home for two weeks, on a number of medications that I started, not just the ketamine and LDN, I hope she will comment on her experience and her progress since flying back to the east coast after her brief visit here.

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It is often essential to taper off opioids to allow other medication to work.

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I feel she was able to benefit from these low doses of medication because she tapered off all opioid medication prior to her visit, thus allowing her system to recover and respond to these medications. We will know more in the next few months as she slowly titrates up on some of the medications that were started.

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Next year on her return, we may be able to withdraw some of the medications depending on how well she is doing.

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Finally, ketamine does cause her to have brief side effects. Her husband likens the effect the same as half a glass of wine: “She’s really cute.” Thankfully, most people have no side effects and if they do, they rarely last more than 20 minutes.

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She sends an update below, 80 to 90% better. Hopefully this will continue to improve over the next months as she slowly increases the medication we started. And ketamine has an additive effect in some. It is anti-inflammatory.

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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.

.

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

~~~~~

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

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Gliopathic Pain — when Neuropathic Pain Treatment Fails


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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.

Abstract

Microglia play a crucial role in the maintenance of neuronal homeostasis in the central nervous system, and microglia production of immune factors is believed to play an important role in nociceptive transmission. There is increasing evidence that uncontrolled activation of microglial cells under neuropathic pain conditions induces the release of proinflammatory cytokines (interleukin – IL-1beta, IL-6, tumor necrosis factor – TNF-alpha), complement components (C1q, C3, C4, C5, C5a) and other substances that facilitate pain transmission. Additionally, microglia activation can lead to altered activity of opioid systems and neuropathic pain is characterized by resistance to morphine. Pharmacological attenuation of glial activation represents a novel approach for controlling neuropathic pain. It has been found that propentofylline, pentoxifylline, fluorocitrate and minocycline decrease microglial activation and inhibit proinflammatory cytokines, thereby suppressing the development of neuropathic pain. The results of many studies support the idea that modulation of glial and neuroimmune activation may be a potential therapeutic mechanism for enhancement of morphine analgesia. Researchers and pharmacological companies have embarked on a new approach to the control of microglial activity, which is to search for substances that activate anti-inflammatory cytokines like IL-10. IL-10 is very interesting since it reduces allodynia and hyperalgesia by suppressing the production and activity of TNF-alpha, IL-1beta and IL-6. Some glial inhibitors, which are safe and clinically well tolerated, are potential useful agents for treatment of neuropathic pain and for the prevention of tolerance to morphine analgesia. Targeting glial activation is a clinically promising method for treatment of neuropathic pain.

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

Source

Department of Anesthesiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.

Abstract

Management of chronic pain, such as nerve-injury-induced neuropathic pain associated with diabetic neuropathy, viral infection, and cancer, is a real clinical challenge. Major surgeries, such as breast and thoracic surgery, leg amputation, and coronary artery bypass surgery, also lead to chronic pain in 10-50% of individuals after acute postoperative pain, partly due to surgery-induced nerve injury. Current treatments mainly focus on blocking neurotransmission in the pain pathway and have only resulted in limited success. Ironically, chronic opioid exposure might lead to paradoxical pain. Development of effective therapeutic strategies requires a better understanding of cellular mechanisms underlying the pathogenesis of neuropathic pain. Progress in pain research points to an important role of microglial cells in the development of chronic pain. Spinal cord microglia are strongly activated after nerve injury, surgical incision, and chronic opioid exposure. Increasing evidence suggests that, under all these conditions, the activated microglia not only exhibit increased expression of microglial markers CD 11 b and Iba 1, but also display elevated phosphorylation of p38 mitogen-activated protein kinase. Inhibition of spinal cord p38 has been shown to attenuate neuropathic and postoperative pain, as well as morphine-induced antinociceptive tolerance. Activation of p38 in spinal microglia results in increased synthesis and release of the neurotrophin brain-derived neurotrophic factor and the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α. These microglia-released mediators can powerfully modulate spinal cord synaptic transmission, leading to increased excitability of dorsal horn neurons, that is, central sensitization, partly via suppressing inhibitory synaptic transmission. Here, we review studies that support the pronociceptive role of microglia in conditions of neuropathic and postoperative pain and opioid tolerance. We conclude that targeting microglial signaling might lead to more effective treatments for devastating chronic pain after diabetic neuropathy, viral infection, cancer, and major surgeries, partly via improving the analgesic efficacy of opioids.

 

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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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