CBD efficacy on nonmotor symptoms of Parkinson Disease anxiety & psychosis


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This is the last section of a review article Managing Psychosis in Parkinson Disease

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Results from preclinical and preliminary studies also suggest that cannabidiol (CBD) has therapeutic potential for nonmotor symptoms of PD.14 The multifaceted mechanism of action as an agonist of 5-HT1A, partial agonist of CB1 and CB2 receptors, and antagonist of the G-protein–coupled receptor GPR55 reverses the iron-induced epigenetic modification of mitochondrial DNA and the reduction of succinate dehydrogenase activity and decreases the levels of the pro-inflammatory cytokines IL-1β, TNF-α, IFN-β, IFN-γ, IL-17, and IL-6—all of which decrease pro-inflammatory mediators resulting in neuroprotective, anxiolytic, and antipsychotic effects.14

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“Several in vitro experiments have demonstrated promising neuro- protective effects of CBD in PD models. In one of these models, using PC12 and SH-SY5Y cells treated with MPP+ [1-methyl-4-phenylpyridinium], CBD increased cell viability, differentiation, and the expression of axonal [GAP-43] and synaptic [synaptophysin and synapsin I] proteins,” Ferreria-Junior and colleagues wrote,15 while acknowledging the paucity of studies that have addressed the biological bases for the purported effects of CBD on PD. “Double-blind, placebo-controlled, randomized trials with larger samples of patients with PD are needed to elucidate the possible effectiveness and mechanisms involved in the therapeutic potential of CBD in this movement disorder. This will also include the putative effects of CBD in preventing L-dopa–induced severe [adverse] effects and preventing PD progression.”

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The endocannabinoid system serves as an important filter of excitatory, inhibitory, and modulatory inputs that act at the midbrain and terminal regions to orchestrate DA neurotransmission by controlling DA cell body firing patterns, terminal release, and effects on postsynaptic sites in the striatum.16 Beneficial effects of CBD administration have been observed prior to or immediately after induction of PD-like symptoms in animal studies, which may suggest a preventive role rather than a therapeutic one.14 In an early open-label pilot study to evaluate the efficacy of CBD on nonmotor symptoms of PD in 6 patients with PDP, psychotic symptoms significantly decreased under CBD treatment, as evaluated by the brief psychiatric rating scale and the Parkinson psychosis questionnaire.17

 

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Psychiatric comorbidities prevalent in the majority of patients with PD are associated with more disease severity, impaired QOL, and increased use of healthcare resources, with longer hospital stays and re-hospitalizations adding to the total cost burden.

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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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Low Dose Naltrexone for Pain


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From NPR: 

In Tiny Doses, An Addiction Medication Moonlights As A Treatment For Chronic Pain

 

Alex Smith

 

Lori Pinkley, a 50-year-old from Kansas City, Mo., has struggled with puzzling chronic pain since she was 15.

 

She’s had endless disappointing visits with doctors. Some said they couldn’t help her. Others diagnosed her with everything from fibromyalgia to lipedema to the rare Ehlers-Danlos syndrome.

 

Pinkley has taken opioids a few times after surgeries but says they never helped her underlying pain.

 

“I hate opioids with a passion,” Pinkley says. “An absolute passion.”

 

Recently, she joined a growing group of patients using an outside-the-box remedy: naltrexone. It is usually used to treat addiction, in a pill form for alcohol and as a pill or a monthly shot for opioids.

 

As the medical establishment tries to do a huge U-turn after two disastrous decades of pushing long-term opioid use for chronic pain, scientists have been struggling to develop safe, effective alternatives.

 

When naltrexone is used to treat addiction in pill form, it’s prescribed at 50 mg, but chronic-pain patients say it helps their pain at doses of less than a tenth of that.

 

Low-dose naltrexone has lurked for years on the fringes of medicine, but its zealous advocates worry that it may be stuck there. Naltrexone, which can be produced generically, is not even manufactured at the low doses that seem to be best for pain patients.

 

Instead, patients go to compounding pharmacies or resort to DIY methods — YouTube videos and online support groups show people how to turn 50 mg pills into a low liquid dose.

 

Some doctors prescribe it off-label even though it’s not FDA-approved for pain.

 

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For discussion of mechanism and case reports of the remarkable efficacy of this anti-inflammatory medication, use search function top left above small photo. Thankfully his insurer is covering the cost of the compounded capsules.

 
 
 
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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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For My Home Page, click here:  

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Anger


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Anger at the failure of our medical system to support research and treatment of pain, anger at failure of the few currently available analgesics, anger at lack of interest or funding from Pharma – it requires at least $10,000,000 more to finish one important human treatment before submitting to FDA – that’s just one study. Pharma does not care, the price is peanuts to them. At one point, a company bought it, intending only to bury it. They do that for rheumatology treatments too, both the innate immune system and the adaptive immune system are being ignored. What could be more powerful than the immune system?

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Anger

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Anger at the failure of most medical organizations to discuss cannabis, medical marijuana. Training in cannabis is imperative.

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I am thrilled that Scripps Memorial Hospital Grand rounds in 10 days is a one hour lecture by the doctor who is head of HelloMD, national leaders in physician approval for medical marijuana, and in education.

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Anger at the destruction of the field of pain management. I posted on this two days ago, top left column. Anger at the greed in the medical system where pharma can buy whatever they want by sprinkling money at congress who will never ever ever do anything about the unholy prices of drugs. Certain elements in power will never stop trampling on the poor and the disabled. They will never treat the addicts. There is no will, they are paid off and nobody wants to help the disabled, the unwell, the poor. Not in  the U.S. Voters do not want to hear it.

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Anger says step back, surrender.

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There is nothing anyone can do. The swamp is exhausting, dirty, dangerous and black.

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I have tried 7-1/2 years to introduce a new paradigm. At various lifetimes in medicine, I have had funding, sat on boards of companies, and panels at FDA. I have witnessed the destruction of what it once was 43 years ago when I entered practice. A long and tortured history, but still the most exciting thing in the world is medicine, science. So what? They shut off the field of pain and are killing it. The world is the world. Always was, always will be. Lust and greed, says the sage. You cannot uncurl the curly tail of a pig, says the sage. Always was, always will be. Do your duty. You cannot escape it. But surrender to love.

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Surrender. Do what you can and surrender the results to the Infinite.

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Read these books:

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Dying to Get High, Marijuana as Medicine

by Wendy Chapkis and Richard J. Webb

NYU Press 2008

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From back leaf:

“How can a substance that is no mystery to half of all adults in the United States prompt such confusion and misrepresentation in the realms of law, medicine, and policy?…. Offering nuance in place of slogans, Dying to Get High tells an inspiring story of the tactics and philosophies of a little-understood health movement.”

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“A beautifully written account from the front lines of the struggle between a federal drug war complex determined to keep demonizing marijuana and the growing movement of patients and doctors who have found marijuana to be a valuable medicine.”

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“….. Provides a human element to the history, pharmacology, psychology, and politics of medical marijuana in a way that no other work has. I loved reading it.”

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Heroin Century

by Tom Carnwath and Ian Smith

Routledge Press, London

2002

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This is an extremely important, amazingly interesting, readable book for everyone.

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From back cover:

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Is heroin really dangerous? Or Is it just dangerous because it is illegal?

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Page-one 93,

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“The income of the drug barons is an annual $254 thousand million dollars, greater than the American defense budget.”

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Read this book. A page turner! Exciting! fast paced, awesome! mind boggling!

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And just because you might flash some anger to propel you to actually do something, don’t get stuck there. Be at peace. Work hard. Use your expertise. Surrender to the Infinite.

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While you are thinking about it, tell Congress to make pain management a mandatory course in more than the current 3% of medical schools, less then 30 hours in 4 years. Fund research and treatment of neuropathic pain such as CRPS, Complex Regional Pain Syndrome because it can be so disabling – the same neuropathic pain can occur from strokes. Don’t we deserve better? Not even cancer pain is taught, let alone grade schoolers who should be taught about the body, about addiction, drugs, sex. Teach all that opioids cause pain because they trigger inflammation in the immune system and that stimulates pain. The more opioid you give, the more the pain. Teach about the brain’s pleasure centers and addiction, how drugs and food and cigarettes work there and how addiction kills.

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Have a wonderful life all of you. There’s a lot of work to take up. You will meet great people. Can’t wait to see what a little anger will do.

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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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Comments are welcome.

This site is not for email, not for medical questions, and not for appointments.

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

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Avoid opioid use in surgery to reduce postop pain


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Science for years has confirmed that opioids trigger inflammation and that creates pain. Trauma and surgery also create inflammation that leads to pain. How logical is it then to continue use of sufentanil for anesthesia when it is the most highly potent opioid 500 to 1,000 times stronger than morphine. Where is the logic in creating pain by using sufentanil as the anesthetic? A new one on the market will be 10,000 times stronger than morphine. Inflammation is not always easy to reset after you strafe the innate immune system with an opioid.

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Why is ketamine not used more often for surgical anesthesia when we know ketamine profoundly lowers the inflammatory response thus reducing pain more than ever. Studies for years have shown that even a small dose of ketamine reduces postop pain. This is not new.

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A study needs to be done comparing patients who receive no opioids. At least this study showed that when fewer opioids are used, pain scores are 37% lower than if more had been given. Patients given higher doses of opioid, had higher analgesic requirements postop. That increases the risk of persistent chronic pain and the tragic risk of addiction.

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Opioids inflict known lasting harm, pain and suffering, perhaps disability and addiction.

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Reduced opioid use in surgery linked to improved pain scores
Written by Brian Zimmerman

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After anesthesiologists at the University of Virginia Health System in Charlottesville began administering fewer opioids to patients during surgeries, patients’ self-reported pain levels dropped, according to a study led by three UVA anesthesiologists.
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For the study, the team examined 101,484 surgeries that took place in the UVA Health System from March 2011 to November 2015. During this time period, the amount of opioids administered via general anesthesia at the system was reduced by 37 percent.
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For the same time period, self-assessed patient pain scores recorded in post-op recovery units dropped from an average of 5.5 on a 10-point scale to an average of 3.8, marking a 31 percent improvement.

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One of the study’s leaders, UVA anesthesiologist Marcel Durieux, MD, PhD, said the impetus behind the pain score improvements is likely attributable to several factors. One, previous research has indicated opioids can ultimately make people more sensitive to pain. And two, the increased use of non-opioid painkillers like lidocaine and acetaminophen during surgeries at UVA was likely effective.

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….”There is very clear evidence that people can become opioid-dependent because of the drugs they get during and after surgery,” said Dr. Durieux. “I think that by substantially limiting opioids during surgery, we’ve made an important step in addressing that problem.”

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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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This site is not for email and not for appointments.

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

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Microbiome, Metabolome & Disease


 

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Many of us have followed the research in this field for health, happiness and well-being. Today’s questions and answers from an expert on microbiota in Reddit Science is of great interest and something I wanted on these pages for future reference. I sifted through the pages to condense the questions, leaving answers intact. AMA is short for Ask Me Anything. Where Professor Barrett’s  responses to questions are clear, I have omitted the questions; where not clear, questions are abbreviated and/or added. I am sure we would all like much more information on inflammation and the inflammasome, the gut and brain and health. Support science. Be careful of low quality journals and quackery. She says even some yogurts have no bacteria.

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Science AMA Series: I’m Kim Barrett, Professor of Medicine at the University of California, San Diego and Editor of The Journal of Physiology. This week, we published an issue on the microbiota [editorial free], so I thought it would be a great opportunity to discuss how our microbes influence our well being. AMA!

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This is her main message, again and again:

[–]Kim_Barrett

Eat a well-balanced diet, including cultured/fermented foods, and avoid excessive fat and processed carbohydrates..

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[–]Kim_Barrett

Thanks to both. There is a lot of epidemiological evidence for the health benefits of all of these fermented foods, which may deliver bacteria similar to probiotics as well as beneficial metabolites that have greater bioavailabilty. These foods have been consumed by humans for millennia but were less prevalent in the diet as society discovered refrigeration etc. But studies to actually prove efficacy and mechanisms of action remain in their infancy. This is an area where the National Center for Complementary and Integrative Health is placing a lot of emphasis for research funding.

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Q Nose/sinuses:

[–]Kim_Barrett

Yes, this is a less appreciated area but rapidly growing area of study. I definitely would encourage you to look at our special issue of the Journal of Physiology, which has short reviews on the oral, skin and vaginal microbiota. Our external cavities all have their own distinctive microbiotas, but in aggregate they may encode many of the same sorts of metabolic capacities as seen in the gut. The specific populations may also depend on the type of environment – for example, the bugs on your forearm are different from those on your forehead. Lots more work to be done.

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there is not a simple way currently of knowing about our microbiota’s composition, but general indices of gut health may give some clues. Likewise, finding effective probiotics may be a bit of a case of trial-and-error, but there is good epidemiological evidence for a beneficial effect of fermented foods like Kombucha.

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Q on IBS:

[–]Kim_Barrett 

Serotonin is a major controller of gut motility and sensation, and alterations in serotonin signaling have been documented in irritable bowel syndrome. The cells that make serotonin in the gut have been shown to express receptors for short chain fatty acids (SCFAs), which are major products of bacterial metabolism of undigested carbohydrates. Finally, some gut bacteria metabolize the serotonin precursoe, tryptophan, which in turn has implications for the production of appropriate gut levels of serotonin.

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Q:  Sometimes, when I am constipated, I can perceive a certain taste and smell that arrives internally. Have direct nerve connections between the bowel and the brain been identified? What role to microbiota play in perception of satiety? What is the importance of the neurological phenomenon vs the blood chemistry in controlling weight gain or loss?

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[–]Kim_Barrett 

Lots of nerve connections between the brain and gut, and gut nerve endings have been shown to sense bacterial metabolites. To the extent that the microbiota and their metabolites control the secretion of GI hormones, they clearly participate in satiety perception, but this still needs further study. And weight gain/loss is such a complex phenomenon, also encompassing societal and behavioral aspects, that the relative contributions of the factors you mention have not been worked out by any means.

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Good and bad may be too simplistic. A “good” bacteria may be bad for you if in the wrong place. As for substrates and products, this is probably too big of a topic to tackle right now, but I would direct you to the work of Eugene Chang at the University of Chicago who has done a lot of work in this area. Gut permeability is also clearly important. We have done work to show that certain commensal and probiotic species can tighten the gut barrier so that pathogens and toxic metabolites are less able to penetrate and initiate inappropriate inflammatory reactions and a vicious cycle of further weakening of the gut barrier.

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Q   Strong evidence correlates aberrations in gut diversity with certain diseases. Phylogentitcally speaking, it seems to matter more that the microbiome is diverse and less important which species are specifically there. The hypothesis being that the gut microbial metabolome is relatively stable, regardless of specific species present. http://go.nature.com/2iQLOu1

Q1 – Have clinicians started to take the next step, looking at disease correlations with perturbation of the microbial metabolome?

Q2 – If so, what have they found? Do probiotics replace those missing metabolic pathways?

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[–]Kim_Barrett 

Absolutely agree with your comments about the metabolome. However, most of this work at present is still in preclinical models, although there has been a lot of attention to the way in which metabolic pathways change after bariatric surgery, for example.

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Q:

When I was very young, I had a few instances of food poisoning visiting family in Mexico, I even contacted tuberculosis. I, of course, was given many antibiotics. I’ve had a lot of digestive issues since then, it was always a problem. I’m 36 now, and adopted a very low carb diet 3 years ago. During the initial transition, I had, to put it succinctly, severe dhiarrea. Like stuff was probably dieing off. And then, 4 months in, I had more energy, metal alertness, and general feeling of being present. And I no longer had crippling depression. From a completely anecdotal standpoint, I think that changing my diet also drastically changed my gut biome, and that, in turn, actually effected my brain function. It seems like what you’re research has shown is that this isn’t some woo-woo thinking, but an actual thing?

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Q does Kefir boost gut bacteria?

[–]Kim_Barrett

Yes, along with other related foods.

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Q are we discovering new categories of bacteria in the body?

[–]Kim_Barrett 

This was a big sticking point in the field initially since many of the bacteria cannot be cultured. Now they are identified by sequencing. The estimate is that healthy individuals harbor at least 1000 different species. Not to mention viruses, fungi, protea….we’re just getting started, and as you imply, the bioinformatics challenges are huge.

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[–]Kim_Barrett 

There’s quite a bit of evidence that mixtures of different bacteria are more effective than single bacteria. Perhaps they have complementary metabolic functions, or mutually help each other to colonize the gut.

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Q  research of healthy bacteria for auto immune disease?  Crohn’s disease?

[–]Kim_Barrett

Others are exploring a role in asthma.

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Q: studies in which obese mice had received gut flora from lean mice and subsequently lost weight, and vice versa. Does this imply that a microbial treatment for obesity in humans could be developed, and if so, is there any interest in this?

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[–]Kim_Barrett 

A lot of people are looking for just such a treatment!

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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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This site is not for email and not for appointments.

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

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Caffeine May Reduce Age-Related Inflammation, Stanford Aging Study


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Caffeine may be able to reduce inflammation.

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Inflammatory immune molecules increase as we age and are associated with mortality from all causes, Alzheimer’s disease, stiffening of arteries, hypertension and cardiac disease. Inflammation kills. Yesterday Stanford and colleagues from University of Bordeaux published results of a long term aging study of 114 patients in Nature Medicine (paywall):

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Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states

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For nonscientists, see below. Caffeine may block inflammation. Adenosine and adenine are known to stimulate the inflammasome. Caffeine blocks the effect of adenosine.

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“They found that older people between the ages of 60 and 89 tend to ramp up production of immune molecules in a complex called the inflammasome. That’s a clump of immune proteins inside cells that activate one of the immune system’s big guns, called interleukin 1 beta or IL-1B. It’s an important molecule for fighting off infection, but too much of it for too long has been linked with chronic diseases like heart diseasecancer, and Alzheimer’s disease.

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Among the older people in the study, 12 of them made much more of these inflammatory molecules, and 11 people made much less. The less-inflamed group was also healthier, with lower blood pressure, more flexible arteries, and more relatives who lived past age 90.

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They also had lower levels of the breakdown products of DNA and RNA circulating in their blood, including one molecule called adenine, and another called adenosine — which is adenine attached to a sugar molecule. These molecules are known to stimulate the inflammasome, and lower levels of them could explain why this group was less inflamed. In fact, treating cells with these breakdown products made them churn out more inflammatory molecules, and made mice more inflamed, with higher blood pressure.

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HIGHER BLOOD LEVELS OF CAFFEINE CORRELATED WITH LESS INFLAMMATION

That’s where the caffeine comes in. Caffeine is known to block the effects of adenosine in the brain — that’s how scientists think it keeps us awake. So, the researchers suspected that it’s possible that it could block the effects of adenine and adenosine on immune cells, too, and reduce their ability to cause inflammation. According to a questionnaire, people in the less inflamed group consumed more caffeinated beverages like coffee, soda, and tea. In fact, higher blood levels of caffeine and other caffeine breakdown products correlated with lower production of inflammatory molecules like IL-1B.

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When the scientists treated cells with adenine and another molecule known to trigger the inflammasome, the cells that were soaking in caffeine produced far lower levels of inflammatory molecules. The researchers still haven’t fully explained how caffeine is interfering with inflammation. And the results aren’t enough to base any behavioral recommendations off of; but it’s comforting news for those of us who were already reaching for that second hit of caffeine, anyways.”

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Many articles on pro-inflammatory cytokines IL-1β, IL-6, and TNF-α are found in the setting of chronic pain and in depression:

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IL-1β is an essential mediator of the antineurogenic and anhedonic effects of stress.

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Depressed rodents shown to have inflammation, published by Yale and NIMH a few years ago.

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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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This site is not for email and not for appointments.

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Ketamine Consensus Statement for Mood Disorders Needed


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I just had a call from a student writing a paper on ketamine. Question #1: What % respond to ketamine.

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Why are we still asking this rather than treating with ketamine?

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3.7% of Americans are disabled with Major Depression, many for decades, or entire lives. Antidepressants may work on only 30%. It’s time we had a consensus statement on use and training of ketamine.

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Read Cornel West: Pity the sad legacy of Obama, before you read on.

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Pity the sad legacy of psychiatry. Even neoliberals fail to speak up, stuck in the dictates of the few. We’ve known for decades that ketamine is effective treatment. It can work in hours. IV ketamine clinics are popping up like Jack in the Boxes and will continue to increase in number.

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It is time to ask: Is IV the only way to administer? Is it cost effective? Do these doctors have the right training?

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We need a consensus statement from psychiatrists and from the American Academy of Psychiatry and Neurology on training in inflammation, the innate immune system and treatment with ketamine.

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Every psychiatrist and mental health specialist should be instructed in rationale, the innate immune system, glia, inflammation, addiction medicine, glial modulators (ketamine is only one), and how to look at the whole system, holistically, not just one more drug. Inflammation, diet, exercise, among these.

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A focus on Ketamine alone in treating a complex organ like the brain is incomplete. Think inflammation, brain, spinal cord, glial modulators, not just drugs, not just ketamine. Ketamine is potentially addicting, a schedule III drug. Evaluate a patient just as you do when prescribing opioids.

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Then we need consensus on its use for intractable chronic pain including RSD/CRPS.

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Why don’t schools teach anything on the human body and the immune systems rather than biology and cutting up frogs?

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 Data below is from National Institute of Mental Health:

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Major Depression Among Adults.

  • Major depression is one of the most common mental disorders in the United States.

  • The 12-month prevalence data for major depressive episode presented here are from the National Survey on Drug Use and Health  (NSDUH). Based mainly on the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), in the NSDUH study a major depressive episode is defined as:

    • A period of two weeks or longer during which there is either depressed mood or loss of interest or pleasure, and at least four other symptoms that reflect a change in functioning, such as problems with sleep, eating, energy, concentration, and self-image.

    • Unlike the definition in the DSM-IV, no exclusions were made for a major depressive episode caused by medical illness, bereavement, or substance use disorders.

  • In 2015, an estimated 16.1 million adults aged 18 or older in the United States had at least one major depressive episode in the past year. This number represented 6.7% of all U.S. adults.

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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.

~~
This site is not for email and not for appointments.

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

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CRPS & All Patients – pills no help for this severe pain


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Yes, people with nerve pain, CRPS pain, any pain, and often those without pain have this. It can lurk for decades before pain is obvious. But find the right spot and you’ve got it. Doctors and patients fail to understand one of the worst disabling causes of severe pain. Pills, drugs fail to help, but doctors reflexively respond with pills because they often have no training in this. The slightest movement, a sudden flicker of being jarred and pain explodes up to a 9. Pain may catch you by surprise, you yelp, you can’t help it, and you stop instantly. It’s unbearable, the slightest jolt, the wrong angle, a split second. Some reach for a handful of pills, and cut back activity until they are completely unable to walk or move without fear. For others, no jolt or yelp, it just appears and silently gets worse without your knowing, until it manifests decades later and now you cannot function. You forget the incident that set it off.

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CASE

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Healthy 19 year old with pain on standing, walking, wanted a motorized wheelchair on first visit

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This young student had suddenly dropped out of UC Berkeley before the end of the quarter due to severe pain, difficulty walking. The only patient in 41 years of medicine who asked for a motorized wheelchair, was only 19, had no medical illness, no neurological deficit, no inflammatory markers, no injury, but unbearable pain on standing and walking.

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After four months of physical therapy, he was pain free and regained full function, out in the park running with his dog and his friends. Nineteen years old and able to live a normal life. It hurts like crazy. Physical therapy had to get out all the “snags” in muscle and fascia that prevented normal function and caused excruciating pain. There is no magic.

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CASE

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A grandmother with pain in both feet had not been able to stand for six long years. She loved cooking for family and grand kids, but was unable to stand to do anything. She could not walk. In less than two weeks of physical therapy, she was walking 1 to 2 miles a day and loving her life again. Depression vanished. Building her strength to walk more each day.

 

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Oh, need I explain that when you taper off opioid in a case like these, yes, they will have pain just from withdrawing the opioid – the body wants its opioid back and taper creates pain that may stay high for weeks even months, until the body stops klanging for its opioid and the psyche stops catastrophizing to figure out it can live without vegetating by sedating the brain. Each cell in the body goes wild for its opioid and does not want to give up its drug. The autonomic nervous system goes into overdrive, patients leave your practice to find any of hundreds of thousands of doctors for more opioid that perpetuate the desire to lie back and do nothing to trigger any slight jolt. Just narcotize the brain.

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CAUSE

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Stasis. Inactivity. Not moving. Immobilization. Sedentary muscle, just sitting, or in a cast or after knee surgery, bedridden. Stasis. Simply stasis. Muscles and fascia develop “knots” that you are not aware of until suddenly, the wrong jolt, the slightest move, and you freeze, screaming in pain. Prolonged sitting often causes hip flexion contractures. “Knots” can be felt in muscle,  tender points are highly localized. P.T. finds them and causes screaming pain to get them out. My own body has it now in several muscles, both thighs. It’s common. They’re quiet until you find them and mash them. It hurts like crazy to treat it, but that’s the only way to get this silent killer that takes lives. Pills do nothing. Blood curdling yelps and bruises appear during P.T. If you don’t do it, it gets worse. They are not always easy to find, not always a “knot” that can be felt, but zingers they are.

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HOW

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What’s in blood besides red cells, white cells, oxygen? Fibrin and collagen. If you cut yourself, fibrin instantly seals the bleed and forms a clot. The body then builds collagen, a major component of connective tissue. What had been soft tissue can turn into a tough fibrous matrix. Nutrients and oxygen cannot get to it. The “knots” must be properly and precisely released by a skilled physical therapist to find them all, to release them all.

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Just this week, a patient with back pain who quit P.T. early, told me she learned to reduce back pain in bed by placing pillows under the knees, two pillows. Perfect! to develop hip flexion contractures that prevent standing erect, thus throwing out the spine and soon a 3rd or 4th back surgery. Undiagnosed, untreated hip flexion contractures are surely one of the major causes leading to preventable spine surgery.

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Doctors don’t know how or perhaps don’t care to diagnose it.

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Pills do NOTHING to relieve it.

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There is no hope until the knots are undone.

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Compliance is crucial. We have a choice. But in 2003, W.H.O reported: 50% of people don’t comply w/ chronic disease management. Insurance denies medications, insurance limits physical therapy, you are left with rapidly increasing disability and a miserable hell that does not respond to pills of any kind, not even massive doses of opioids.

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STASIS – OBESITY

 

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Obesity leads to increasing stasis. Let’s not dwell on obesity in itself that causes inflammation and increases estrogen production in fat all over the body – that’s one of the reasons obese men develop breasts. Every woman knows estrogen can cause horrific disabling pain. The more fat we pack on is like adding estrogen producing ovaries all over the body. And fat cells remain hungry for 10 years before new ones arise. We take to walkers and wheelchairs instead of the obvious: lose weight, take pounds of fat off joints, muscles and spine, rid the system of excess pain-producing estrogen, and then work out the knots with physical therapy. Thin people get knots in muscle too but obesity and its load of estrogen is a big culprit.

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Motorized wheelchairs:  How many obese individuals are willing to lose weight, even when it means regaining life and use of body? You don’t have to pay money to eat less. Exercise helps but it is not the only way to lose weight, and people may eat more after exercise.

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Seize the day. Failure is not a healthy option but I’ve chosen favorite foods too often. Eat well, nothing between meals, limit protein to 4 oz of fish/chicken/meat or 8 oz dairy/legumes, one piece of fruit in AM with protein, add loads of veggies – 5 cups per day, the low glycemic veggies, one tablespoon oil/butter with each meal. Never skip meals. Plan ahead, carry your own food if you work away from home. Most of all, avoid anything that is high glycemic. Stomach will feel very full, but very eager at the time of next meal. You will find your mood is stabilized. Your joints will not bother you as much or not at all.  You will have more energy and less depression.

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If you are unsure what foods are considered high glycemic, use the old axiom for weight loss “if it’s white, don’t bite” with some exceptions such as cauliflower. Here is a link to a list of glycemic food levels to get you started.

 

 

 

 

 

 

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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.

~

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

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The advertising below is not recommended by me.

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NFL – Prevent &Treat Chronic Traumatic Encephalopathy, CTE – Opioids Blamed Wrongly


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Crowdfunding Needed

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Prevent and Treat

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Chronic Traumatic Encephalopathy

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C.T.E.

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Opioids Wrongly Blamed

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Leagues may have known about this technology since 2002 publications

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Football players have demonstrated ability to influence others

and raise money for important medical causes.

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This is not about class action law suits.

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This can be imaged early and likely treated.

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It’s about science and bringing medicine into the 21st century.

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A paradigm shift began with the discovery

of the innate immune system by internationally recognized scientists in 1991.

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The clock has been turned off.

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We can change this now.

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Funding is needed for internationally recognized leaders to continue this work.

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The tragic deaths of former NFL football players from repeated concussions has led to brain damage and death from Chronic Traumatic Encephalopathy (CTE). Suicide profoundly shocks us when many players like Junior Seau at age 43 and now Tyler Sash, die at age 27. He is the youngest found to have such extensive brain damage, as bad as that seen in Junior Seau. So much can be done with state of the art science now that has been ignored.

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Disclosure: I was asked by a research institute if I would evaluate retired NFL players. I chose not to do that so that I might be free to post unbiased information that is not subject to being manipulated by either side in the ongoing appeals for compensation that must be going on with the NFL for $70 million. Tragic that this is such a fight. Even more tragic, this may be diagnosed early and treated.

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Pearls

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Fear of compensation claims after concussion injury prevents imaging of football players and veterans early, while still treatable, before severe changes and death.

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Fear of compensation claims has prevented decades of research funding by internationally recognized scientists. Could politics at NIH & the VA have turned off funding for veterans with pain and with concussion blast injuries? Does cancer and heart disease forever lock up all the research money and now it shifts to stem cells?

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It is inaccurate to say that CTE cannot be diagnosed except after death at autopsy.

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PET scan imaging of glia can show changes early, while alive.

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The ligand PK1195 must be used for PET scan to image glia, available for years in Australia, not yet in America.

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FDA approval must be obtained for the ligand PK1195 before it is used to  image glia in the United States.

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CTE can be diagnosed early.

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CTE is likely to be treatable.

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Internationally distinguished scientists have shown reversal of complete paralysis in rat models of multiple sclerosis in 2010, a so called “degenerative” neurological disease.

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Intractable pain and treatment resistant depression can be put into remission with glial modulators. Surely CTE and other neurological diseases can be approached with scientifically recognized mechanisms and treatments – even if doctors are not aware of the paradigm shift and how to modulate neuro-inflammation. See years of posting on this site since 2009 based on the most important finds in the field of neuroscience for more than 100 years: the innate immune system, glia, neuro-inflammation, and ability to use glial modulators, to modulate intractable conditions that are known to lead to suicide and/or death.

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Paradigm shifts in all fields including medicine, fail to be recognized.

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CTE gives opioids a bad name and misled Taylor Sash and likely others from the diagnosis of CTE that caused years of severe forgetfulness and behavior changes. He may have chosen suicide by opioid.

 

 

 

FACT:

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Trauma such as concussion or infection or stroke triggers inflammation in the brain:  “cytokine storm”

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Inflammation kills brain cells

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Inflammatory cytokines (inflammation) are produced by glia that has been activated by trauma or other causes such as infection, stroke, etc.

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Activated glia produce neuroinflammation and cell death.

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Inflammatory cytokines produce pain and “degenerative” neurological and psychiatric disorders including dementia, depression, anxiety, delirium and death.

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Neuro-inflammation in brain has been found in teens with early signs of schizophrenia, in rats made depressed, and rodents with chronic pain.

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Glia have been detected in life, in vivo, with PET scan imaging, by internationally-recognised radiologist working at Imperial College London, now based in Australia.

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PET scans require a ligand, PK1195, approved for years in Australia – must be approved by FDA in the United States before it can be used here.

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There is good clinical data and publications in animal models to show that damage in brain and spinal cord produced by activated glia can be reversed.

E.g., In 2010, total paralysis has been completely reversed in a rat model of multiple sclerosis by internationally-recognised glial researcher who, in 1991, transformed the understanding of glia that comprise 85% of the brain, since then known to be the innate immune system.

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Publications have shown that patients with major depressive disorder and patients with chronic low back pain have memory loss and brain atrophy.

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Opioids cause pain by stimulating production of inflammatory cytokines that are known to damage neurons in brain and spinal cord – and must be tapered off. We have better treatment for pain.

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Insurance carriers routinely deny payment for recognized medications and procedures to relieve pain.

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CDC is planning a nationwide experiment to radically limit opioids.

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Treatment with glial modulators that reduce neuroinflammation has been shown clinically to relieve treatment resistant major depressive disorder, PTSD, bipolar depression and intractable pain. They are neuroprotective.

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We need to be able to flag players off the field early and intervene with treatment such as glial modulators either before, during or after repeated injury.

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GOALS

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1.  PK1195, a ligand for PET scans, must be tested and approved by FDA. Approval is mandatory for all medications or substances injected into vein or body.

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It simply “tags” the PET scanner to image glia, the cells of the innate immune system that are activated by trauma, infection, stroke, etc.

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2. Do serial PET scans using PK1195 to image glia in NFL players and veterans after blast injury.

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Trauma from concussion is causing cytokine storm, killing brain cells –> ultimately end stage dementia, anxiety, depression, suicide

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3. Flag that player off the field. Follow glial changes during treatment to determine if able to return or if permanent, but prior to end stage damage.

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4.  Treat with glial modulators preventively, early, middle, and/or late

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This subject will be continued. My apologies for lack of time to delete and edit. Days pass by quickly to post brief comments. Time is limited. Please send comments, below.

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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.

Relevant comments are welcome.

If any questions, please call the office to schedule an appointment.

This site is not email for personal questions.

~~~~~

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

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Please be aware any advertising on this free website is

NOT advocated by me and NOT approved by me.

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Be the change you wish to see – or walk away. Money at NIH


 

 

A Turning Point

 

$$$$$ MONEY $$$$$

 

at NIH

 

May not come this way again

 

NIH developing

5-year NIH-wide Strategic Plan

 

 

 

Donate to organizations, below

They can provide feedback to NIH via the

RFI Submission site


 

 

 

John C. Liebeskind, 1935 – 1997, distinguished scholar and researcher, past president of the American Pain Society, had the radical idea that pain can affect your health.

 

Research decades ago by an Israeli team at UCLA and others had shown “that pain can accelerate the growth of tumors and increase mortality after tumor challenge.” Decades ago Professor Liebeskind lectured all over the country: Pain kills.

 

He wrote an editorial in 1991, summarizing a life’s work:

 

“Pain and stress can inhibit immune function.”

 

 

Quoting John Bonica, the father of modern pain management, he wrote:

 

“Bonica has long argued that the term ‘chronic benign pain’ (used in distinction to pain associated with cancer) is seriously misleading.  Chronic pain is never benign, he contends; “it is a ‘malefic force’ that can devastate its victims’ lives and even lead to suicide.”

 

 

Liebeskind continues, “It appears that the dictum ‘pain does not kill,’ sometimes invoked to justify ignoring pain complaints, may be dangerously wrong.”

 

Pain mediates immune function

 

Importantly

 

  Opioids mediate the suppressive effect of stress on natural killer cells,

 

 published in 1984, immune system.

 

Alcohol increases tumor progression, 1992, immune system.

 

It used to be news.

He did not live to see change.

 

People just want to go on doing what they’re doing.

They want business as usual.

 

 

After 1991, we saw the great discoveries of neuroinflammation, pioneered by Linda Watkins, PhD, the early understanding of the innate immune system, its involvement in chronic pain and depression, and a few weeks ago, a British team showed neuroinflammation in teens with early signs of schizophrenia and DNA markers.

 

 

Major Depression has the same neuro-inflammation found in chronic pain, often responding to same medications, in particular glial modulators – immune modulators. Now, perhaps early schizophrenia will respond to glial modulators, reducing inflammation seen on scan in teens, before they become homeless and burned out by antipsychotic drugs

 

Inflammation out of control destroys neurons

 

Fire on the brain

 

 

We must be the change we wish to see

 

It’s not just the Bern. It’s been starting. Forces are finally coming together. We want change. It’s been too much. Too long.

 

We won’t take it anymore.

 

I figure if I tell you about it, you might just mention it to someone to pass it on. That is all. One small action may lead to change. Activate inputs to the NIH strategic plan.

 

 

~ Action needed ~

 

Prices of drugs becoming unaffordable

No new drugs for pain or major depression

Research to repurpose existing drugs

Expose the politics destroying our compounding pharmacies

 

Above all

The #1

Major Priority:

Request NIH to solicit priority call for research on

Glial modulators of the

Innate immune system

 

 

Why?

 

Glia modulate

chronic pain, major depression

and almost every known disease

 

Glia are your innate immune system

 

Inflammation kills

 

 

 

 Stress kills. Inflammation kills.

 

 

Pain kills

 

In the 1970’s, Professor Liebeskind and an Israeli team at UCLA injected cancer cells to two groups of rats that had sham surgery. Cancer spread much faster and killed far sooner in the group with poor treatment of surgical pain.

 

 

~ Pain kills ~

 

He lectured all over the country

 

Forty five years ago

 

 

I’m gonna be dead before I see this country do anything but unaffordable opioids and the magical ineffective trio of gabapentin, Lyrica, Cymbalta to treat chronic pain. The devastating, blind, nationwide emphasis does nothing to address the cause: inflammation, the innate immune system gone wild.


 

 

Innate immune system in action

 

Untreated pain suppresses the hormone systems too.

 

Untreated depression – same inflammation kills lives.

 

Where’s the money?

 

We are the change we wish to see. It’s pitiful I am so lazy. Suddenly, too late, we may need something, but, aha, no new drugs in the pipeline.

 

 

 

~ Make a joyful cry to NIH ~

 

They are soliciting input from professional societies

 

If your condition has failed all known drugs for pain or major depression, then make a joyful cry to NIH, now, before they give away all that nice new $$$$$money$$$$$.

 

 

Follow and join

 

American Pain Society

 

 

International Association for Pain

celebrating 40 years of pain research

 

 

Reflex Sympathetic Dystrophy Syndrome Association

help for CRPS/RSD  

 

 

 

The key to CRPS/RSD pain will apply to all forms of chronic pain, in particular the most difficult form, neuropathic pain. RSDSA funds research into all forms of chronic pain, not only Complex Regional Pain Syndrome (CRPS/RSD). Their scientific board members are not funded by opioid money.

 

 

 

Exactly

what is the annual cost of care

as fraction of GDP

for the growing population of Americans on opioids

for one year, for lifetime?

 

 

People are dying from prescription opioids and those who need them find they don’t work well enough. Prescriptions opioid costs must be a huge fraction of the medical costs in the United States GDP. You are required  to see a doctor every single month each year, often lifelong, just for one opioid, 12 months a year x 30 years x tens of millions of people and increasing – a growth industry. Not even counting $600 a day for the opioid, what the cost of monthly visits for 30 years? Not counting the army of DEA, FDA, CDC agents watching the opioids like a hawk. We all have to be sharp, addiction is growing. Addiction aside, deaths from prescription opioids are shaking up the CDC forcing urgent change this coming month.

 

 

 

Opioids do not work well for chronic pain

We need better

It’s not just the $600/day price

They just don’t work

 

 

donate

 

 

Raise a joyful noise at NIH now or write back at us readers with comments and better suggestions. Tell others what you’d like to see. Which politicians do you know would be most interested in this at national levels and organizations?

 

You may never see this change unless you do it now. Other forces will get this new money.

 

 

Turning point now

May not return

 

 

We are at a turning point and we will fail to catch the sail that’s coming fast to carry all research money in their shiny big stem cell direction. They never look back.

 

 

There is so many medications we can use today, FDA approved drugs that can be re-purposed and applied to recent cutting edge science. Someone must pay to do the work to study this.

 

 

Re-purpose old drugs

 

 

Stanford just showed a popular generic drug improved recovery of stroke paralysis in mice to begin at 3 days rather than 30. Old drug, new purpose, of course more years of testing to confirm in humans. Brilliant team applying new science.

 

 

Request
NIH to solicit a

Special Invitation

for 30 good protocols to

repurpose old drugs

 

 

Hundreds of old drugs, already approved, could be involved in mechanisms we have recently learned about. Speak up or money will go to shiny new stem cells. None for chronic pain or major depression. No company will find this profitable – it must be funded by NIH. A popular generic sleeping pill can bring astonishing return from stroke paralysis.

 

 

Congress has not opened this new money to NIH in many long years. How often will there be extra money?

 

 

donate

 

 

Lawrence A. Tabak, D.D.S., Ph.D.
Principal Deputy Director, NIH, solicits you to

Review the NIH Strategic Initiative Plan and their

Request for Information (RFI) and the NIH website

and provide your feedback via the RFI Submission site

 

 

This is for “stakeholder organizations (e.g., patient advocacy groups, professional societies) to submit a single response reflective of the views of the organization/membership as a whole. We also will be hosting webinars to gather additional input. These webinars will be held in early to mid-August.

 

 

 

Be the change you wish to see

Donate to those organizations

to solicit the change you wish to be

 

 

 

Happy New Year

Rejoice!

There’s money at NIH

 

 

 

 

 

 

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.

Relevant comments are welcome.

If any questions, please schedule an appointment with my office.

This site is not for email.

~~~~~

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

 

 

 

 

Dementia, Memory Loss, Brain Atrophy – not always Alzheimer’s Disease. We are all at risk.


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Dementia

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Alzheimer’s Disease

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Sustained Reversal Published by UCLA

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If you have a medical problem that involves the brain, this may apply to you.

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In a major breakthrough, Dale E. Bredesen reported that 9 of 10 patients with Alzheimer’s Disease were able to return to full time work. His report appeared in the journal Aging, September 2014. A PDF can be downloaded. He is UCLA Augustus Rose Professor of Neurology, director of the UCLA Easton Center Center for Alzheimer’s Disease Research.

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He used a 36 point holistic approach based on published neuroscience research. There is no drug. .

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There is No Magic Bullet – Highly Individualized

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Dementia is the third leading cause of death in the U.S. behind cardiovascular disease and cancer. It affects roughly 25 to 30 percent of the population over 80, with 70 percent of those having Alzheimer’s Disease.

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The number of cases doubles every 5 years in people over 65. By age 85, almost half of all people are afflicted. A family history of Alzheimer’s increases risk. Five percent have onset early in age.

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In other words, once we pass 60, we are all at risk for this disease, but may occur as young as 30 in rare cases.

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What to do?

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1. See a good neurologist for a proper diagnosis. If  dementia, there are at least 9 causes, Alzheimer’s is 40% of those [N.B. source, verify].

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Some are treatable, such as deficiency of vitamin B12 or thyroid. Remember, do not take folic acid unless you are taking adequate B12 as folate will mask B12 deficiency and lead to neurological problems that may be severe.

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2. Read the Alzheimer’s Disease In-Depth Report in the New York Times. It gives clear and comprehensive advice for the patient and the caregiver. It is not a diagnosis.

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3. Memory loss can be reversed and sustained. Dr. Bredeson reports, “Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement.”

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He points out the failure of the so called Alzheimer’s drugs, that help little or not at all. Instead, he uses a 36 point metabolic approach, discussed in more detail below. He said the findings are “very encouraging,” but he added that the results are anecdotal, and a more extensive, controlled clinical trial is needed.

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Alzheimers has the potential to devastate the economy worldwide in the near future. The Bredesen report is a first. Ideally it may revolutionize medical research, fiscal budgets, dietary guidelines, policy changes, school lunches, advertizing and foods that promote all the wrong changes in brain. But it involves changing behavior and even simple school lunch programs that improve cognitive function and health have been mercilessly attacked.

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Alzheimer’s Disease is relentless. The causes are not known and there is no cure. Changing behavior is dificult.

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There are three hallmarks of the diagnosis of Alzheimer’s Disease:

  • amyloid plaques

  • neurofibrillary tau tangles, the primary marker

  • loss of connections in the brain

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Plaques and tangles may be present for years and may appear quite early in life, without ever developing Alzheimer’s. We do not have a specific marker for diagnosis, but we can exclude treatable conditions. More importantly, doctors and families need a better tool to monitor cognitive decline so that we may intervene early before the devastating and costly disease captures the lives and finances of patients, caregivers and families alike.

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Risk Factors For Alzheimers Are The Same As For Heart Disease

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Obesity, inactivity, smoking, diabetes, hypertension, hyperlipidemia, low Vitamin D – serum level of 50 ng/mL is ideal.

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Benzodiazepines increase risk of Alzheimers 50%, reported in 2014, particularly with long acting forms (Valium, clonazepam) or long term use. They are widely prescribed for insomnia or anxiety, yet almost 50% of older adults continue to use these drugs. It is unrealistic to think they can be eliminated – they are habit forming after all, but a Quebec study showed that a brochure alone helped 27 percent of elderly users taper down and discontinue their drug in six months. Another 11 percent reduced dosage. Do taper off slowly with proper guidance. Informed consent can help each person to choose the risk or the taper. If the brochure doesn’t scare you, I don’t know what will.

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Systems Approach – No Silver Bullet

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The small trial published by Dr. Bredesen showed reversal of cognitive decline using an individualized 36 point ‘systems approach’ to memory disorders. Results started to be seen after 3 to 6 months.

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In the UCLA Newsroom interview, he says: “The existing Alzheimers drugs affect a single target, but Alzheimers disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well, he said. The drug may have worked, and a single hole may have been fixed, but you still have 35 other leaks, and so the underlying process may not be affected much.”

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It “involves comprehensive diet changes, brain stimulation, exercise, sleep optimization, specific pharmaceuticals and vitamins, and multiple additional steps that affect brain chemistry.” Though each target may be affected in a modest way, the overall effect may be additive or even synergistic.

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The downside is its complexity. No one was able to stick to the entire protocol. The side effect was improved health and improved body mass index. Successful candidates did lose weight. He emphasizes that this small study needs to be individualized and replicated on a large scale. The program for one patient included:

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  • eliminating all simple carbohydrates, gluten and processed food from her diet, and eating more vegetables, fruits and non-farmed fish

  • meditating twice a day and beginning yoga to reduce stress

  • sleeping seven to eight hours per night, up from four to five

  • taking melatonin, methylcobalamin, vitamin D3, fish oil and coenzyme Q10 each day

  • optimizing oral hygiene using an electric flosser and electric toothbrush

  • reinstating hormone replacement therapy, which had previously been discontinued.

  • fasting for a minimum of 12 hours between dinner and breakfast, and for a minimum of three hours between dinner and bedtime

  • exercising for a minimum of 30 minutes, four to six days per week

 

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Diet

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We have known that calorie restriction reverses amyloid deposition.

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One diet was developed by nutritional epidemiologist Martha Clare Morris, Ph.D., of Rush University in Chicago, and her colleagues.

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According to the findings, the MIND diet was able to lower the risk of AD by as much as 53 percent in participants who strictly adhered to the diet, and by about 35 percent in those who followed it fairly well. It was compared to the DASH diet and Mediterranean diet.

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“To follow the MIND diet, a person should eat at least three servings of whole grains, a salad and one other vegetable every day —  along with a glass of wine —  snack most days on nuts, eat beans every other day or so, eat poultry and berries at least twice a week, and eat fish at least once a week.

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However, a person should limit consumption of the designated unhealthy foods, especially butter (less than one tablespoon a day), cheese, and fried or fast food (less than a serving a week for any of the three), to have a real shot at avoiding the devastating effects of AD, according to the study.

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Berries are the only fruit included in the MIND diet. “Blueberries are one of the more potent foods in terms of protecting the brain,” Morris said, and strawberries have also performed well in past studies of the effect of food on cognitive function.”

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I recommend that my patients Google pro and anti-inflammatory foods and move their diet in the direction of lowering the burden of inflammation.

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Supplements

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CurcuViva or Longvida is a special formulation of curcumin, the active ingredient in turmeric spice that is able to cross through the blood brain barrier and reach the brain. I posted on it here and it is reviewed in more detail here. Turmeric does not enter the brain. It was developed by researchers at UCLA Alzheimer’s Research Center showing the relationship between pre-tangle tau, brain cell death, and cognitive function. Full memory was restored in mice that had dysfunction caused by tau tangles. It has been shown to help Alzheimers and joint pain.

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WARNING: Do not take CurcuViva if ulcers or gallbladder disease.

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Supplements Can Harm – Caution Toxic

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Supplements can cause great harm. Many are toxic and deplete the brain of essential nutrients or cause irreparable harm.

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Always research the value and harm of every supplement put into your body. The best site on herbs and botanical I have found is updated regularly by the expert in integrative medicine and alternative therapies at Memorial Sloan Kettering Cancer Center. They research supplements and herbs to show efficacy and how they interact with prescription medications to verify if they may help or harm. Ask, does this drug – yes, vitamins and supplements are drugs but unregulated and untested – cause toxic increase in medication or rapid loss (speeded metabolism) of prescription medications resulting in less effective serum levels and no benefit.

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Metabolism of drugs and drug-drug interactions is critical to know.We do not have enough data on supplements. We ignore behavioral changes such as diet, exercise, stress reduction at our peril in favor of unregulated, unproven, costly silver bullets.

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Reflecting the importance of my interest in supplements since the majority of Americans take so many, one of the first things I did in starting this website is to post on benefit and harms of vitamins and supplements.

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In addition to that detailed list, use the search box just above my photo top left to find other posts on frequently used supplements mentioned below.

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The Good, The Bad and The Ugly

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  • Vitamin B6 in excess can cause irreversible neurological disease – know the safe dose because it is now overdosed in many things.

  • Heavy NSAID use increases risk of Alzheimers.

  • Zinc blocks copper that is essential for every cell in the body.

  • Vitamins A and E have no proven benefit and serious risks.

  • CoQ-10 is essential for every cell. Statins deplete CoQ-10. It is essential in the electron transport chain to make ATP, the energy used by every cell. Research has shown it helpful for mitochondrial diseases such as migraine and Parkinsons Disease though very high doses for the latter. I do not know of any publications for its use in Alzheimers.

  • Fish oil can reduce triglycerides 45%. Adjust dose based upon level of triglycerides – elevated levels increase risk of Alzheimers.

  • Hormones affect function of many organs including brain. If low, then restore at least to low normal. If high, rule out tumor.

  • Low vitamin D doubles the risk of dementia and Alzheimers.

Low Vitamin D Doubles Risk of Dementia & Alzheimers Disease

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That was published in the journal Neurology, August 2014. Vitamin D is a special category and I have posted on its anti-inflammatory and analgesic benefit many times, its effect on the immune system, on pain relief, and on depression. It is important for five cancers, heart disease. Again, use the search function top left by my photo for details.

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WARNING: Make sure before taking any Vitamin D that your MD checks PTH and then if normal, recommend a dose of D3 based upon serum levels of 25(OH)D. I maintain my patients on a serum level of ~50 ng/mL, not more, not less, in accord with the most recent research.

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B Vitamins

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Brain atrophy occurs in those with aging as well as with Major Depression or Chronic Pain and with aging. They were able to prevent 90% atrophy of the hippocampus and areas targeted by Alzheimers Disease with specific doses of B vitamins, below. The OPTIMA (Oxford Project to Investigate Memory and Ageing) at Oxford University, March 2013. I disagree with their dose of Vitamin B6 as I have seen tragic toxicity in patients that takes at least one year to reverse, if ever.

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These are the doses I suggest:

  • .B12 500 mcg/day

  • Folic Acid 800 mcg/day

  • B Complex —-B6 not to exceed 2 mg ! B6 is one of the vitamins in B Complex and it

    can be toxic to nerve. It is being overdosed in many supplements and energy drinks.

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Inflammation

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If you haven’t gathered by now, the focus is on inflammation. The brain and spinal cord has an innate immune system different than the immune system in the rest of your body. The cells of the innate immune system are called glia, and they produce many chemicals, in particular, microglia and astrocytes produce cytokines. Anti-inflammatory and pro-inflammatory cytokines. They must be in balance.

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Inflammatory cytokines are shown to be involved in almost every known disease including Alzheimers, Parkinsons, ALS, MS, autoimmune disease, chronic pain, major depression, cancer, atherosclerosis.

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Pro-inflammatory drugs: opioids and alcohol for example.

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Anti-inflammatory drugs: low dose naltrexone, dextromethorphan, ketamine, amitriptyline, Vitamin D, melatonin. Again, use the search function above photo for the many posts including case studies. It would be helpful to see more medications studied to show if they are pro- or anti-inflammatory, and to see studies on these medications in persons with memory difficulty. That will not happen since they are generic, low cost.

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Living Wills & Healthcare Power of Attorney

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Be aware of the changing laws in your state. In the event dementia prevents you from choosing your care, if you have asked that no food or water be given, medical staff are not legally permitted to follow that directive. Legal precedent directs that if you reach for food or water, that indicates your intent to be fed, regardless of written requests made when you were of sound mind. It behoves us all to change behavior now.

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Summary

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  • Use an Alzheimers self test for early detection. This is not a diagnosis.

  • Obtain a neurological evaluation.

  • Be aware of the importance of the 36 step metabolic approach.

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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.

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

~~
This site is not for email and not for appointments.

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

~~~~~

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

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Please ignore the ads below. They are not from me.

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Proposal: A 5-Year Study of Best Methods to Treat Intractable Pain


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PROPOSAL

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A controlled trial to improve care for chronic pain:

The study to understand prognoses and preferences for

outcomes and risks of treatments

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..

 

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Model after Joanne Lynn’s 1995 SUPPORT Study

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A controlled trial to improve care for seriously ill hospitalized patients:

The study to understand prognoses and preferences for

outcomes and risks of treatments (SUPPORT)

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Proposal

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A controlled five-year trial to improve care for outpatients with chronic pain. The study will be designed to understand prognoses and preferences related to the outcomes and risks of various treatments.

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The focus:

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Intractable pain, those who have failed pain medications and procedures or those with moderate to severe pain who only partially respond.

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Study polypharmacy, compare medications that may show synergy or that additively improve relief.

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Study and search for glial modulators – medications that reduce proinflammatory cytokines.

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Problem

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Research is needed to give persons with intractable pain the data and the confidence that they can affordably use to choose the best treatment needed to get their lives back again. They have already spent tens of thousands. They may be unable to work. We all need these options.

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There are a few small islands in this country doing a radical experiment in managing pain without opioids [narcotics, the police term] as discussed in the New York Times in May 2014, and the 2008 Mayo Clinic study. Efforts such as these need to be supported with data as soon as possible in order to reduce the burden of disability and pain in our society, especially our youth, our children, our veterans, our aging seniors, well everyone. We can be productive and we want to be.

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I have seen remarkable outcomes, pain that failed to respond to all known pain medications, going into partial and even total remission, lives restored after weaning off opioids and appropriate treatment given.

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We cannot expect any medication to work every time. How often can we achieve better results after opioids are tapered off? Opioids may prolong pain in Complex Regional Pain Syndrome where remission seems possible only after they are stopped, yet opioids may be essential in many forms of chronic pain. We need data on the radical experiment to manage pain without opioids, and determine how best to manage chronic pain with them.

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Opioids have a long history of being the drug of choice to treat chronic intractable pain by doctors who lack information and training about other exciting options now coming to the fore. Compounding the problem is the fact that physicians do not know how to diagnose musculoskeletal pain and do not know how that good physical therapy is actually effective.

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Healthcare providers need data about all the options to begin to address the toll that chronic intractable pain exacts and government worldwide need to know what is cost effective and possible. Many countries cannot obtain opioids.

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We must not be insensitive to the financial burden that frustrates patients when they spend tens of thousands of dollars for drugs that provide little if any benefit.

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Investment in developing nonopioid treatments for pain does not even begin to compare to the investment in opioids for pain. The few medication choices we have are not enough. Often they fail to help. Expensive drugs are not the best choice if they are not affordable or they are limited to diabetic neuropathy when more than 100 types of peripheral neuropathy have been identified, plus many more types of even more severe neuropathic pain not classified as neuropathy. Shall we continue to ignore all those because FDA has classed these few new drugs for diabetic neuropathy exclusively?

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Let me be clear, prescription of opioids is justified and they are valuable. Opioids are on the World Health Organization list of ten essential drugs. BUT there is little or no research on treatment of intractable pain without opioids.

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Neuropathic pain, nerve pain, is the most difficult to treat. Neuropathy, radiculopathy, transverse myelitis, adhesive arachnoiditis, central pain, RSD, Guillain-Barre, trigeminal neuralgia, Tic Douloureaux, post herpetic neuralgia, to name a few. It is not enough to limit research of neuropathic pain to diabetic neuropathy when it fails to address all other causes. When FDA approves a drug only for diabetic neuropathy, insurers deny the drug for the other 95% of you without diabetes. Insurers may choose to read guidelines as mandates, fiats,  marching orders.

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Neuropathic pain is not the only concern. Physicians do not know how to diagnose musculoskeletal pain. How can they if only 3% of medical schools teach pain management and when doctors do not know how to assess ineffective physical therapy when they have never seen better.

A patient dislocated her hip 7 times, manually repositioned each time in ER. The 6th surgeon impinged a wide band of muscle in the joint causing muscle all down the thigh to bulge 5 to 7 mm high, of rock hard spasm with intense relentless pain. The 7th surgeon had the gentle ability to restore position and release the entrapment. A light touch across the thigh even through clothing can detect the cause. Would a surgeon have discovered to release the entrapment unless she had dislocated a 7th time? Simple muscle strain, undiagnosed by a surgeon who deals with muscle all the time, was not even noticed and he ignored the acute pain it caused. She has now learned how to avoid dislocating that new hip. Had the muscle not been appropriately identified as cause, she would not be able to move by now. But the surgeon should have had the skills to notice instantly before those muscles became chronically strangled. She was referred for manual physical therapy and thankfully, before all else could occur, she dislocated and was repositioned by the 7th surgeon. A wonderful teaching case for a teaching hospital that should be every hospital. Grand Rounds for pain cases.

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MAJOR FUNDING DECLINE IN PAIN RESEARCH

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 BEFORE 2008

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 BEFORE CONGRESS CUT NIH BUDGET BY UNTHINKABLE 30% IN 2010

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Perhaps the biggest impediment to gathering data about pain management is the lack of government funding for pain research and lack of a Pain Institute at NIH. If not, funding will continue to be fragmented and split elsewhere, not to learn about one of the most costly problems in every society.

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In 2008, before the worldwide depression, pain research was in major decline. The AAAS, the American Association for Advancement of Science told us then:

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“Federal funding for pain research is declining sharply, more than 9 percent a year since 2003, according to a new study published in The Journal of Pain. Pain research, as a result, now accounts for only 0.6 percent of all grants awarded by the National Institutes of Health (NIH), despite the high prevalence of chronic pain in the U.S.

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“This startling finding shows the government’s meager investment in pain research is seriously out of proportion with the widespread chronic pain incidence in our society, which is estimated at one in four Americans and accounts for more than 20 percent of all physician office visits,” said Charles E. Inturrisi, president of the American Pain Society and professor of pharmacology at Weill Cornell Medical College, New York. “And this disparity is not attributable to years of budget cuts at NIH because the Journal of Pain study clearly shows pain research has a higher percentage decline than the overall NIH budget. So the drop in agency funding has not affected all research areas equally.”

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[emphasis mine.]

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Research in pain was sharply declining prior to 2008. Then a 30% cut across the board in 2010. Thank the American Pain Society for those ancient 2008 figures. No one had ever asked – which is why we need a Pain Institute at NIH.

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Frustration is compounded the last few years by insurers no longer willing to authorize many opioids and non-opioid medications, even generics.

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As for the cost of opioids,  a single opioid for one patient may exceed $80,000 per month when the patient is required to use with another long acting opioid, and often several nonopioid adjuncts just to bring pain down from 9 on scale of 10, to a slightly more bearable 7 or 8 which is severe, relentless and prevents sleep and ability to concentrate. One drug that costs pennies to make, sells for $80,000 a month to allow 4 a day when at least 6 a day are needed and it is only one of many for pain every day.

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Prescription of opioids is justified and may be invaluable.

but there is little or no research on

 treatment of intractable pain without opioids.

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We need national consensus guidelines based on data

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We must do a better job treating intractable pain. We need guidelines that have more to offer than the few opioids and few adjuvants we now have, so few in number, so great the need. Can we know when is it true that opioids are indicated? Our use is many times more than all the other First World countries?

 

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Treatment must be individualized

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Data is needed to guide choice

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Compounded Medications are among the

most useful drugs we have for treatment of intractable pain

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Compounded medications may be the only ones that help, and can reduce pain to zero. We can re-purpose the delivery of any medication, as long as it has been FDA approved. But the last few years insurers have been discontinuing coverage for compounded medications and Medicare has never covered them.

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This must change. Who is funding that political blockade that denies coverage for compounded medicine? The cost may be $120 for one compounded medication vs $80,000 for one opioid. Either way, the person with intractable pain likely needs 3 or 4 or 5 or 6 medications, compounded or not. Who can afford $400 per month out of pocket for compounded medications that work, when insurance will not cover the affordable drugs. Who can afford that out-of-pocket expense if insurers cover nothing for your pain, neither the bright shiny opioid or the compounded sprays, capsules, suspensions, creams, troches, as well as the essential solutions instilled into the bladder for interstitial cystitis?

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This must change. Lawmakers must be called to account for allowing and perpetuating the inhumane taking advantage of those who suffer intractable pain.

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A first step in getting lawmakers to pay attention is to amass a body of compelling data.

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BALANCE IS NEEDED

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The United States as a society cannot afford for pain research to die and go bankrupt and leave only opioids as the standard treatment for hundreds of types of pain. Someone has to begin the needed studies. It does not just bankrupt the patient, it leaves us all bankrupt, the country most importantly. It ends marriages, tears apart families. To be struck down as a child with intractable nerve pain the rest of your life, or be struck in your prime, is devastating. And disability gets routinely denied for pain. Why? Perhaps because pain is taught in only 3% of university medical schools. How are doctors to imagine that pain can end lives when they have no experience seeing how disabling it can be?

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 If doctors cannot see the devastating toll that pain takes,

how can we expect accountants to see it?

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The Study We Need

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Solution

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 To gain a comprehensive and compelling picture of how pain impacts the population and how to effectively treat it we need a large-scale study:

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  • Five years in duration

  • 10,000 outpatients – statistically this must be adjusted to obtain multiple outcomes

  • At five major university teaching hospitals for regional differences

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 Outcomes

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The study will yield important information about the following:

..

  • Efficacy

  • Pain Numeric Rating Scores, Percent Improvement

  • Functional Improvement, etc

  • Compounded medications

  • Racial and Gender Disparities

  • Addicts who have chronic pain

  • Top notch manual physical therapy* [see below], not for what passes in most places. This must change ASAP. United States is far behind other countries. Even if the condition is neuropathic, it often becomes musculoskeletal after splinting for months, years

  • Interventional procedures

  • Meditation

    How you brain can heal your body and your body heal your brain.

  • Pain changes DNA, neurotransmitters. Have we permanently changed them with opioids?

  • Polypharmacy. When employing one drug alone is unlikely to lead to a successful outcome.

  • Stem cells for joint pain – autologous lipid derived mesenchymal stem cells

  • rTMS, experimental after 20 years, is it still better for acute than for chronic pain?
    Who will benefit, for how long? How many weeks of relief for that $15,000 investment?

  • Glia, the Innate Immune System

Opioids create pro-inflammatory cytokines that create pain and opioid tolerance.

Restore cytokine balance, reduce inflammation and pain.

Which of our existing medications either trigger or reduce inflammatory cytokines in the CNS?

  • Pain in the person with Alzheimers dementia

  • Danger of combining opioids with benzodiazepines

  • Danger of long term use of opioids (regardless if short or long acting)

  • Appropriateness of using opioids as a first choice in acute pain (loss of a milk tooth, sore throat in a teenager, acute back pain, ankle strain, etc.)

  • Appropriateness of opioid holidays.

  • Post op pain can be avoided completely with combined use of oral low dose naltrexone and ketamine IV anesthesia. Patients discharged directly from recovery room with no need for pain medication for months or years

  • Cost Benefit Analysis

 

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Five Conditions Will Be Studied

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Strong emphasis must be placed on neuropathic pain that so often fails to respond to any intervention

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1. Complex Regional Pain Syndrome

The Netherlands invested €25 million over 5 years to study this one devastating pain condition, far out of proportion to the incidence in that small country. There are pain specialists who cannot recognize it and/or doctors who routinely deny disability for this devastating pain, like death in life.

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2. Low Back Pain

Define criteria for surgery.

If we wait too long before surgery is done, will we ever reverse the chronic pain that has set in?

Have we condemned that patient to monthly visits for opioid the remaining 50 years of their life?

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3. Other neuropathic pain conditions such as adhesive arachnoiditis, trigeminal neuralgia, transverse myelitis, Tic Douloureaux, Post Herpetic Neuralgia, Interstitial Cystitis, Vulvodynia, Proctalgia, Pudendal Neuropathy


4. Painful peripheral neuropathy nondiabetic and Painful Small Fiber Neuropathy  all forms of painful neuropathy

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5. You choose – central pain?

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What We Must Do Now

 

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  • Find a pain advocate like the cancer advocate of the 1950’s that changed attitudes for research

  • Fund the pain SUPPORT study

  • This will spin off enormous research ideas that we must begin separately to implement with research as each develops, the need is beyond urgent. How many more years can we make everyone wait?

  • Write letters, to congress, the White House. Real letters, not email, not signature lists. Congress will not hear us unless we speak in very, very large numbers.

  • Help the topic of intractable pain become a part of the 2016 presidential conversation.

  • Incentivize teaching hospitals to teach pain management and to develop options for nonopioid treatment of chronic intractable pain. Pain is a multidisciplinary field, not limited to Anesthesiology procedures.

  • Create an Institute for Pain Management in addition to the 28 institutes at NIH, three of which are for addiction, none for pain. Pain is the number one reason people seek medical help.

  • Require that pain specialists sit on the FDA advisory committees for pain medication – none recently.

  • Require insurance coverage for compounded medications.

  • Prevent FDA from limiting medication to cancer pain.
    Cancer pain does not exist.

    There are basic types of pain that occur in persons who have cancer, neuropathic pain being worse than other forms of “cancer pain.” It has the same medication response or failure to respond as persons whose pain is not due to cancer.

  • How do we restrict the use of opioids to severe pain when there is nothing else to offer and after everyone is started on opioids by their family doctor years before they see a pain specialist?

  • Novel and ancient methods for treatment of pain should be explored including cannabis and possibly hallucinogens

  • Isolation of pharmacologically important medicine from rainforest and deep seas must be done before they disappear.

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Physical Therapy is the #1 Key to Chronic Pain

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Manual Physical Therapy was introduced to the United States in the late 1970’s but is rarely practiced or not done well. It does not mean “hands on.” It derives from techniques brought to us by British Commonwealth and Scandinavian countries. Our healthcare providers do not know how to differentiate between good and useless practices. Fortunes and lives are wasted hinging on that distinction. Pills never can undo the harm brought about by common musculoskeletal issues – and our providers have no training in recognizing simple muscle trigger points, let alone intractable connective tissue contractures. My patients have been misdiagnosed as histrionic, drug seeking, personality disorders, and worse. It boils down to ignorance and lack of basic training, let alone believing what the patient says and not having the tools to help.

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The trend is for year long residency programs following the 3 year Doctorate of Physical Therapy (DPT).  The year long residency program is a very positive step.  The limitations are that it is a year with a clinical staff that may have a specific perspective.  The push towards evidence based practice is a reasonable step but should not exclude considerations of outside the box treatment options.

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The osteopathic manipulative technique has been a cornerstone of best education for physical therapists.  The craniosacral approach is an offshoot from that tradition.  When we get to visceral mobilization, the evidence is much harder to produce but that does not have me shy away from its application.

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Movement is critical for the hormonal regulation of the body.  Chronic stasis leads to numerous changes that compound an underlying medical diagnosis.  We see that with a 16 y/o female, Lyme’s disease, CRPS diagnosis, bedridden for years.  She is significantly benefiting from stretching dysfunction and improving axial extension.  Another who quit walking had global lower limb connective tissue contracture.  Walking is currently limited by soft tissue contracture through the tarsal tunnel, affecting the plantar nerves and the burning and tingling with walking greater than 5 minutes at a time.  Mobilizing the soft tissues will ultimately restore function. This 20 year old quit college due to pain and one first visit requested motorized wheelchair and Social Security Disability. This young person will walk again.

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There is no end point to this educational process except when we think we know it all.  No certification, no degree, no one course signifies competency.  Ongoing intellectual curiosity is the most important element in preparation.

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Prescription painkiller overdose epidemic in the U.S.

Not in other countries

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Pain Management centers at major universities closed in 1991. They lose money, are time consuming, require team conferences that are not reimbursable. Thus began the era when prescription opioids took off for noncancer pain, and no one was generating nonopioid approaches to chronic pain. Anesthesiologists shifted to procedures – that is their focus after all. Procedures are not applicable to many types of pain.

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“Since 1999, the amount of prescription painkillers prescribed and sold in the U.S. has nearly quadrupled, yet there has not been an overall change in the amount of pain that Americans report.”

from the CDC report of prescription painkiller overdose epidemic

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I feel I have failed when I have to point out to my own patient whose pain is severe, that the high dose opioid I have prescribed is not helping, or is creating pain; when I know there are other options which are not available because the FDA has not approved them or because they are prohibitively expensive. I have failed when so many medications I prescribe are not on the formulary.

 

We need a mandatory formulary available for those with intractable pain.

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There were 16,651 deaths from prescription opioids in the U.S.in 2010, “Starting with 4,030 deaths in 1999….” “…nearly 60 percent of the drug overdose deaths (22,134) involved pharmaceutical drugs. Opioid analgesics, such as oxycodone, hydrocodone, and methadone, were involved in about 3 of every 4 pharmaceutical overdose deaths (16,651).” It’s far higher now. A CDC report stated that one in every 20 U.S. adults has a history of [opioid] use – not abuse, but use.

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Monitor risk, yes, but that should not get all the investment. Many addicts would not be there if there were better treatments for pain, if they had not been given opioids after a minor procedure or injury that is better treated with real therapy, not drugs.

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People with pain do not mention the pain has taken their lives. We may see them as weak. That young child with fractures on the ball field is going to need the best care so pain does not become chronic. Give him or her opioids and opioids cause pain, pain becomes worse, intractable before the 6th grade. That is not an addict, but that child and his or her parents are often treated like addicts, at least with suspicion, drug seeking. What is best for that child with chronic pain when she becomes pregnant? When nursing? Think of our young veterans, some with 3 or 4 different pains, and each type addressed differently. What if either of them was an addict before the pain? If we don’t treat them, they will turn to drugs. What are the best, most efficient, options for treatment of intractable pain? When will we learn? We need to identify and treat before it becomes chronic.

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Chronic pain can be reduced or eliminated in many situations now even possibly without drugs, provided the issue is properly identified – and that will never happen until providers are educated in how to identify first class physical therapy. Further research will help to release persons with intractable pain from the prison that too often makes them feel that life is unbearable and that they can more easily face death. We all need to wake up to this situation.

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If we continue to passively allow nothing to be done, then there may be nothing to help us when we fall into the sudden bind of intractable pain when we wake up one day with shingles or a pinched nerve or when pain of the face prevents us from eating or sleeping or speaking or even wanting to live. It will be too late.

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Sharp like a razor’s edge is the path,
The sages say, difficult to traverse.

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Shall we let those we love hang on the edge while we fail to move this multi-tentacled monster forward? How do we light the fire that enables us to solve this fearful fragmentation of choices?

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See how beautifully it works when the right combinations are brought together?

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Yellow rose blue hibiscus

 

 

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

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

~~
This site is not for email and not for appointments.

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

~~~~~

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

.

Please ignore the ads below. They are not from me.

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Intranasal Ketamine in Major Depressive Disorder


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Physicians at Icahn School of Medicine at Mount Sinai, New York, studied intranasal ketamine in 18 patients with Major Depressive Disorder, published in 2014:

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A Randomized Controlled Trial of

Intranasal Ketamine in Major Depressive Disorder

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Conclusions

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“This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.”

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I have previously posted more detail on this study. They report a significant antidepressant effect occurred as early as 40 minutes in some. I have seen some respond in seconds. But the dose is unique and specific to each person and there is no response until that dose is reached.

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It is hoped that more studies will be funded, though that seems unlikely since congress slashed the NIH budget in 2010 by the unthinkable 30%, never done in history.

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Entire generations of scientists are now lost forever.

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Ketamine Safety

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Ketamine is one of the safest medications I have prescribed in 40 years of medicine. And I meticulously obtain laboratory studies at least twice a year to verify any potential harm as it has been reported in addicts that it may affect bladder, kidney, liver or biliary system. I first prescribed ketamine about 14 years ago for intractable pain rated 10 on a scale of 10 for 30 years; and prescribed ketamine since Spring 2012 for Major Depression. For years I searched to find a spray with a metered dosing system. Thus since late 2011, intranasal has been the delivery I find most useful. When given as nasal spray or under the tongue, not swallowed, it goes straight to the bloodstream, bypassing the liver, and works for depression because the liver does not convert it to a different metabolite.

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Nevertheless, it is important to stress that ketamine must be monitored for any possible adverse effects including toxicity and/or addiction. I require long distance patients to be followed by a psychiatrist or psychologist regularly while on ketamine. So far, my returning patients have been stable for years.

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Further, when given by the nasal or sublingual route, I do not see the side effects that my anesthesiology colleagues see after I.V. infusion. I’ve been in board meetings with some of the finest anesthsiology pain specialists in the country sharing and comparing experience. I don’t see those complications. But that is what is published and I.V. is how it is given in the few centers where ketamine is used for treatment of Major Depression or Bipolar Depression.

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Ketamine is a short acting medication whether it is given I.V. or nasally or under the tongue. But it is quite bitter and most prefer nasal delivery.  Review the case study of the professional who traveled out of state once or twice weekly for one year to receive I.V. ketamine. She had failed ECT 9 or 10 times – memory loss was so bad she got lost in her own neighborhood. She now does very well on a small dose every 48 hours given nasally. In the same post, I reported the patient with Juvenile Bipolar Disorder, Fear of Harm phenotype whose profound thermoregulatory abnormalities respond in seconds to ketamine, with a very small dose of 10 mg nasal spray every 3 days. That’s it! Temperature responds in seconds, and the depression responds in 10 minutes in her case.

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Unfortunately research protocols require the study of fixed dosages in order to be a cost effective study for one sample size at one dose to be even slightly meaningful, even then 18 patients studied at Mt. Sinai is a small study at the one dose they used.

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The principle that I have always used is “start low, go slow.” That allows for the discovery that some large men may require the tiniest dose and some tiny 90 pound seniors may require some of the largest doses I’ve seen. It cannot be predicted by body weight. Anesthesiologists generally think in terms of mg/kg body weight, for example the 0.5 mg/kg I.V. generally used for depression. But ketamine’s dosage variance is unrelated to weight. That likely explains why some develop frightening symptoms when given IV, and others do not respond. One size does not fit all. That method either under-doses or overdoses.

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There are case reports on this website giving examples of some individuals I have seen with Major Depressive Disorder. One man is unusual in needing a small dose only every 6 to 8 weeks, but most use the nasal spray daily or every second or third day. I suspect that after initially starting ketamine on a daily basis for one or two weeks, the frequency of dosing may be lowered to every two or three days. Less is more.

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Professor David Feifel at UCSD guesstimates that ketamine helps 70% of persons with Major Depression. I think that’s a fair statement given that we are unlikely even to see the unknown number who remain at home, forever feeling they are unable to leave their confinement. We know that effects of ketamine are blocked in mice that are deficient in BDNF. We may speculate that when ketamine fails in persons with Major Depression, that may be due to lack of BDNF. We know exercise helps Major Depression and exercise increases BDNF. Much more research is needed.

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The use of ketamine is essentially a first line drug for Complex Regional Pain Syndrome (CRPS). That may never be said in publications, but that has been the case for years in persons with CRPS who have failed all other medications. I specialize in CRPS, a form of neuropathic pain that leads to suicide more often than any other pain syndrome.

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For pain, intranasal ketamine is far shorter lasting, typically three hours, rarely six. And requires doses far higher than for Major Depression or Bipolar Depression. Even then, when used for pain six times daily in very high doses, it has proven to be profoundly safe with few if any side effects that last less than half an hour, if present at all.

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Inflammation

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The role of inflammation and glia in the pathogenesis of depression has been well established since 2000, and discussed here. The study of ketamine has taken on new life with the discovery that it profoundly lowers pro-inflammatory cytokines produced by microglia. Inflammatory cytokines have been shown to be elevated in chronic pain and in Major Depression. That is why I feel it is important to prescribe adjuncts that also lower inflammatory cytokines. And patients with Major Depression and Bipolar Depression have reported the adjuncts make ketamine stronger and last longer. Some don’t even need ketamine after awhile, but remain on the adjuncts.

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Ketamine is not a cure and I find it is best used with adjunct medication. In my experience, ketamine and adjunct medications are likely to help as long as prior to treatment, patients are still able to function, to work at least somewhat. I do have 4 patients in the last four years who have not left their home or their bed for many years, and they failed to respond. Sadly, one older woman had to be institutionalized for life, her melancholic depression was so deep. When ketamine is even partially effective, I have patients who had been too fatigued to work before treatment, yet who are able to return to graduate school for a PhD and do well for years on a stable dose. It is immensely rewarding to be a part of this unique therapy, to see them regain life and function after years of misery and disability.

 

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Studies

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S-Ketamine

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It is my hope to be able to compare S-ketamine, that is not yet FDA approved, with the racemic* ketamine that we now have, that was FDA approved in 1970 in high dose as an anesthetic. Obviously we do not use high anesthetic doses for control of pain or Major Depression. I understand unfortunately that when clinical studies are completed, S-ketamine will be available only in emergency departments.

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*Racemic means the molecule has equal amounts of left and right-handed enantiomers (mirror images) of a chiral molecule (meaning, you cannot superimpose the left hand with the right hand. They mirror but do not superimpose). Thus both left and right racemic ketamine mixture has been FDA approved, but the S-ketamine, the left sided molecule is considered a different drug, and must be FDA approved.

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Without FDA approval, ketamine can be studied with FDA permission that provides an Investigational New Drug (IND) application.

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Given the lack of funding for almost any research in this country, I would consider doing a patient-funded study if patients showed interest. It would be modeled on the intranasal study published in the Mt. Sinai study, above, i.e. short term, randomized, double blind, placebo controlled.

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It is reported that S-ketamine may be more effective with fewer side effects. This must be proven and cannot be taken at face value without several studies. Shockingly, some publications in recent years have been fabricated and woven into mythology.

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Finally, ketamine is off-label for pain and for major depression.

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Papolos et al have published Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype

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“Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.”

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PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
Ketamine is a controlled substance.
Administered improperly, or without the guidance of a qualified doctor,
Ketamine may cause injury or death.
No attempt should be made to use Ketamine
in the absence of counsel from a qualified doctor.

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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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This site is not for email and not for appointments.

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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Please ignore the ads below. They are not from me.

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Ketamine – small doses work in depression and bipolar disorder


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Everyone is very edgy right now with depression. Media is sensationalizing, which is the worst thing to do. I even hesitate to write this now.

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Ketamine really does work

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Small doses may be all that’s needed. Even large doses are safe.

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Two Cases

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I hate to play on emotion that is strong right now, but Robin Williams might be alive today if his doctors prescribed ketamine nasal spray.

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Every one, doctors and patients alike, worry about ketamine. It sells newspaper headlines and distorted media coverage that then overtakes the life saving stories of its profound safety when used under good medical supervision. Experience helps.

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Two cases from yesterday and today really must be shared. These two patients would not be alive today if they did not have ketamine nasal spray for their depression.

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I don’t mean to say every one will respond to these extremely tiny doses, but it’s always exciting to hear the effective dose is simply so small.

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These details would make good case reports if time permitted, but there is never enough time. I wanted simply to say a few things now because these two patients were seen.

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**1**

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In May 2014, saw a fifty-ish woman who is now responding to 20 mg (4 nasal sprays) given as one dose every 48 hours. She has been treated at well known university psychiatry departments, failed ECT 9 or 10 times – memory loss was so bad she got lost in her own neighborhood. Received IV ketamine once or twice weekly for one year before I saw her.

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Diagnoses:  dysthymia as long as she can remember, and 25 years of Major Depressive Disorder, PTSD, anxiety, etc. Olympic level athlete —

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**2**

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Second patient now in late teens, Juvenile Bipolar Disorder/Fear of Harm phenotype, profound thermoregulatory changes respond in seconds to ketamine, dose of 10 mg nasal spray every 3 days. That’s it! Temperature responds in seconds, and the depression responds in 10 minutes in her case. She was so violent before treatment that she had been hospitalized 7 times in 2-1/2 years. Doing very very well. And the low dose naltrexone, by the way, is involved in thermoregulation.

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I should mention, no side effects whatsoever. I have never seen toxicity. I watch kidney and bladder function meticulously, and patients with massive pain on very high doses have never had any organ toxicity.

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NEURO-INFLAMMATION AND GLIA – brain on fire.

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I mention Olympic athlete because so many people I see with Complex Regional Pain Syndrome – the pain that so often leads to suicide, seems to occur more often in top level athletes, either state or national level, professional or sponsored in their teens. Yes, they occur in others, but there is a striking predominance in athletes for unknown reasons.

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Glia are triggered by trauma, then they become activated and produce pro-inflammatory cytokines. Inflammation is out of balance. Ketamine profoundly reduces the pro-inflammatory cytokines, and so does low dose naltrexone. I write about these mechanisms with more frequency that anything else. This is what we must address – the brain is essentially “on fire.” And this inflammation, these pro-inflammatory cytokines, are involved in almost every known disease: Alzheimer’s disease, Parkinson’s disease, ALS, chronic pain, major depressive disorder, cancer, autoimmune disease, and atheroscloerosis.

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Inflammation kills. Unfortunately this new research on glia and inflammatory diseases, these diseases could be called gliopathies, all based on new research since the turn of the century. We now know glia are your innate immune system in brain and spinal cord. They need a balance the anti-inflammatory cytokines with the pro-inflammatory cytokines. Inflammation may be lifesaving when you have caught a virus, but not as a steady diet. Give the brain a break or it leads to hyperexcitable glutamate that triggers calcium flooding into the neuron, cell death, brain atrophy and memory loss. Seen in people with Major Depression and those with chronic low back pain.

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Do doctors know about the innate immune system? or the receptor that won the Nobel Prize 2 and 1/2 years ago? or glia?

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Answer: no.

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Papolos et al have published Clinical experience using intranasal ketamine in the treatment of pediatric bipolar disorder/fear of harm phenotype

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Ketamine administration was associated with a substantial reduction in measures of mania, fear of harm and aggression. Significant improvement was observed in mood, anxiety and behavioral symptoms, attention/executive functions, insomnia, parasomnias and sleep inertia. Treatment was generally well-tolerated.

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Dr. Papolos’ video on treatment points out, ketamine nasal spray is off-label

for Bipolar Disorder. And I add, ketamine is off-label for pain and for major depression.

He posts this:

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PUBLIC WARNING

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Public Warning: Ketamine is a controlled substance.

Administered improperly, or without the guidance of a qualified doctor,

Ketamine may cause injury or death.

No attempt should be made to use Ketamine

in the absence of counsel from a qualified doctor.

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“Off label” means it is FDA approved for another purpose, but he prescribes it for Juvenile Bipolar Disorder. I would add that in qualified hands, ketamine is one of the safest medications we have in our formulary.

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More later, as time permits.

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PUBLIC WARNING

reprinted with permission of Demitri Papolos, MD
.
Ketamine is a controlled substance.
Administered improperly, or without the guidance of a qualified doctor,
Ketamine may cause injury or death.
No attempt should be made to use Ketamine
in the absence of counsel from a qualified doctor..

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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.

.

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

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.

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Palmitoylethanolamide “PEA” – Review of Anti-inflammatory, Analgesic, Neuroprotective Mechanisms


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A review of palmitoylethanolamide, or PEA, has been published this June by Mireille Alhouayek and Guilio G. Muccioli from the Bioanalysis and Pharmacology of Bioactive Lipids Research Group, Louvain Drug Research Institute, Bruxelles, Belgium.

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The authors review the impact of PEA on inflammatory and neurodegenerative diseases, and show that inhibiting the breakdown of PEA (the hydrolysis) may increase levels of PEA. This could lead to treatment of inflammatory and neurodegenerative diseases.

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To address the loss of PEA that occurs in various diseases we must either

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1.  replace the decreased levels of endogenous PEA that is made by the brain by taking a capsule such as PeaPure,  a food supplement that contains 100% palmitoylethanolamide, to reconstitute the needed levels

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2.  inhibit the breakdown (hydrolysis) of PEA.

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.I directly quote palmitoylethanolamide4pain that has outlined key quotes from that scientific review:

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They start outlining the focus of the paper:

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Our focus here is on PEA, which is a known anti-inflammatory compound with analgesic, neuroprotective and antiallergic properties.

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Important for understanding the therapeutic relevance of PEA is the next remark:

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Evidence suggests that PEA metabolism is disturbed during inflammation, and that a decrease in PEA levels contributes to the inflammatory response.

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This explains why it is so useful to administer exogenous PEA as a supplement during states of chronic inflammation. Decreased PEA levels induce more inflammation and a vicious circle has started. Administering PEA (for instance as PeaPure capsules of 400 mg, a foodsupplement) can stop this circle and help the organism to restore the PEA levels and decrease inflammation.

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PEA’s mechanism of action

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The next quote is related to PEA’s main mechanism of action:

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Although it is now clear that PEA is a ligand for PPAR-a, some of its effects occur through as yet unidentified receptors.

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Although there are many ways PEA acts in the cell, the PPAR-a receptor indeed seems the most important one; through that receptor PEA can downregulate overactive inflammatory responses.

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PEA levels also decreased following sciatic nerve constriction injury or ligation of the sciatic nerve in spinal cord and brain areas involved in nociception

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PEA levels are not only decreased during chronic inflammation, also during chronic pain states, such as in sciatic pain.

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The fact that an anti-inflammatory treatment restores PEA levels reinforces the role of PEA as an anti-inflammatory mediator.

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PEA levels can be restored also by treatment with classical anti-inflammatory compounds such as NSAIDs, this however triggers many side effects and that can be avoided by treating with PEA itself!

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PEA as a protective molecule

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In the brain, PEA levels seem to be increased following injurious stimuli, and this has been proposed as a homeostatic mechanism aimed at counteracting inflammation and blunting the inflammatory response.

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PEA has self-reparative properties and indeed can be defined as the molecule of self-reparation and self-protection.

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This ‘pro-homeostatic’ increase, although probably slowing disease progression, seems insufficient to exert anti-inflammatory effects in itself, and should be further amplified…

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One of the classical ways to amplify PEA is to administer it as food supplement: start dose is 1200 mg/daily and in cases of insufficient response we suggest to double the dose.

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Although the first identification of PEA as an anti-inflammatory compound occurred more than 50 years ago, general interest in its anti-inflammatory and analgesic properties was not sparked again until the mid-1990s.

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It was due to the work of the Nobel laureate professor Rita Levi-Montalcini that the scientific community understood the importance of PEA in the 90s. However, as patents on this natural compound were not possible, no great interest emerged, as pharmaceutical companies were uninterested. It was due to the work of small companies, such as Epitech Srl and JP Russell Science that PEA was brought to the attention of the general public.

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Mechanism of action in addition to the PPAR receptor

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The authors nicely summarized the effects of PEA:

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PEA inhibits phosphorylation of kinases involved in activation of pro-inflammatory pathways, such as mitogen-activated protein kinase (MAPK), c- Jun N-terminal kinase (JNK) and extracellular signal-regulated kinases (ERK), and the nuclear translocation of the transcription factors nuclear factor (NF)-kB and activator protein 1 (AP-1) and prevents degradation of the inhibitory IkB-a, which when associated to NF-kB prevents its nuclear translocation.

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Besides reducing inflammatory cells activation and recruitment, PEA modulates the expression of enzymes involved in pro-inflammatory processes, such as COX-2 and inducible nitric oxide synthase (iNOS) and reduces nitric oxide and pro-inflammatory cytokines production in vitro and in vivo.

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Relevance for Alzheimer, Parkinson’s and MS

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The neuroprotective effects of PEA are in part the result of its effects on downregulating the inflammatory cascade. Indeed, many neurodegenerative diseases are associated with a strong inflammatory component, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) or MS

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The follow stating:

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This neuroinflammation is no longer simply considered as a consequence of neurodegeneration, but might be a primary factor in some cases; therefore, anti-inflammatory treatments might represent interesting therapeutic strategies in these diseases

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After discussing modern pharmaceutical ways to block the hydrolysis of PEA with pharmaceutical new compounds, they end their overview with an important statement:

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The potential of using PEA as a beneficial endogenous bioactive lipid in the setting of inflammation is well established

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My thanks to palmitoylethanolamide4pain for the outline of key points in this review of PEA.

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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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Neuroimmunology’s Future – Bioelectronics Treats TNF Diseases – Will replace drug industry


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This is an earth changing, once in a century paradigm shift in medicine.

TNF Alpha Diseases

Bioelectronics reduces TNF alpha

Inflammatory Diseases treated without drugs.

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A novel therapy, never done before, is now in clinical trials with Rheumatoid Arthritis patients and it is working well  – with no medication. Electrical stimulation is reducing TNF-alpha, the inflammatory cytokines that underlie many diseases including pain, cancer, autoimmune diseases and major depression. This is a completely new field of medicine reported by The New York Times Magazine. I strongly recommend reading the entire article as I have only a small clip below.

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Several of the foremost neuroscientists are involved with this, starting with the research of Kevin Tracy in 1998 who proved that stimulating the vagus nerve with electricity would alleviate harmful inflammation. He is a neurosurgeon and President of the Feinstein Institute for Medical Research in Manhasset, N.Y.

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Today researchers are creating implants that can communicate directly with the nervous system in order to try to fight everything from cancer to the common cold. “Our idea would be manipulating neural input to delay the progression of cancer,” says Paul Frenette, a stem-cell researcher at the Albert Einstein College of Medicine in the Bronx who discovered a link between the nervous system and prostate tumors….

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The list of T.N.F. diseases is long,” Tracey said. “So when we created SetPoint” — the start-up he founded in 2007 with a physician and researcher at Massachusetts General Hospital in Boston — “we had to figure out what we were going to treat.” They wanted to start with an illness that could be mitigated by blocking tumor necrosis factor and for which new therapies were desperately needed. Rheumatoid arthritis satisfied both criteria. It afflicts about 1 percent of the global population, causing chronic inflammation that erodes joints and eventually makes movement excruciating. And there is no cure for it.

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In September 2011, SetPoint Medical began the world’s first clinical trial to treat rheumatoid-arthritis patients with an implantable nerve stimulator based on Tracey’s discoveries. According to Ralph Zitnik, SetPoint’s chief medical officer, of the 18 patients currently enrolled in the ongoing trial, two-thirds have improved. And some of them were feeling little or no pain just weeks after receiving the implant; the swelling in their joints has disappeared. “We took Kevin’s concept that he worked on for 10 years and made it a reality for people in a real clinical trial,” he says….

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…The biggest challenge is interpreting the conversation between the body’s organs and its nervous system, according to Kris Famm, who runs the newly formed Bioelectronics R. & D. Unit at GlaxoSmithKline, the world’s seventh-largest pharmaceutical company. “No one has really tried to speak the electrical language of the body,” he says. Another obstacle is building small implants, some of them as tiny as a cubic millimeter, robust enough to run powerful microprocessors. Should scientists succeed and bioelectronics become widely adopted, millions of people could one day be walking around with networked computers hooked up to their nervous systems. And that prospect highlights yet another concern the nascent industry will have to confront: the possibility of malignant hacking. As Anand Raghunathan, a professor of electrical and computer engineering at Purdue, puts it, bioelectronics “gives me a remote control to someone’s body.”

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Glaxo has also established a $50 million fund to support the science of bioelectronics and is offering a prize of $1 million to the first team that can develop an implantable device that can, by recording and responding to an organ’s electrical signals, exert influence over its function. Instead of drugs, “the treatment is a pattern of electrical impulses,” Famm says. “The information is the treatment.” In addition to rheumatoid arthritis, Famm believes, bioelectronic medicine might someday treat hypertension, asthma, diabetes, epilepsy, infertility, obesity and cancer. “This is not a one-trick pony.”

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…The subjects in the trial each underwent a 45-minute operation. A neurosurgeon fixed an inchlong device shaped like a corkscrew to the vagus nerve on the left side of the neck, and then embedded just below the collarbone a silver-dollar-size “pulse generator” that contained a battery and microprocessor programmed to discharge mild shocks from two electrodes. A thin wire made of a platinum alloy connected the two components beneath the skin. Once the implant was turned on, its preprogrammed charge — about one milliamp; a small LED consumes 10 times more electricity — zapped the vagus nerve in 60-second bursts, up to four times a day. Typically, a patient’s throat felt constricted and tingly for a moment. After a week or two, arthritic pain began to subside. Swollen joints shrank, and blood tests that checked for inflammatory markers usually showed striking declines.

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Koopman told me about a 38-year-old trial patient named Mirela Mustacevic whose rheumatoid arthritis was diagnosed when she was 22, and who had since tried nine different medications, including two she had to self-inject. Some of them helped but had nasty side effects, like nausea and skin rashes. Before getting the SetPoint implant in April 2013, she could barely grasp a pencil; now she’s riding her bicycle to the Dutch coast, a near-20-mile round trip from her home. Mustacevic told me: “After the implant, I started to do things I hadn’t done in years — like taking long walks or just putting clothes on in the morning without help. I was ecstatic. When they told me about the surgery, I was a bit worried, because what if something went wrong? I had to think about whether it was worth it. But it was worth it. I got my life back.”

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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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Prostate Cancer – Exercise Cuts Inflammatory Cytokines IL-6 & IL-8, reduces psychological distress


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American Society of Clinical Oncologists (ASCO) in Chicago yesterday report on exercise reducing psychological distress. Whether cancer outcome will be impacted is not yet known and will require study but inflammation may impact cancer progression.

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The usual treatments change metabolism, cause weight gain, “loss of lean muscle mass, change[s] lipids, increase[s] rates of diabetes, and it thins bones.”

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Exercise is even more critical in those undergoing hormone therapies.

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This was a small randomized study for seven weeks.

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Patients receiving usual care experienced a 0.08 log10 increase in pro-inflammatory interleukin-6 production, while patients treated with an exercise program experienced a 0.03 log10 decrease in IL-6 (P<0.05), said Charles Kamen, PhD, research assistant professor at the University of Rochester Medical Center in New York.

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In his oral presentation … Kamen and colleagues observed a similar relationship with another pro-inflammatory cytokine, interleukin-8. In the control patients, the researchers noted a 0.03 log10 increase compared with a 0.04 log10 decrease among the exercise group, Kamen said.

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Using the Profile of Mood States (POMS), the research team determined that psychological distress decreased 5.17 points among the exercise group but increased 2.43 points in the patients who were in the usual control group (P=0.02).

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“This study supports the use of exercise for cancer patients for reducing psychological distress and suggests a potential biological mechanism by which this improvement occurs, namely by reducing systemic inflammation,” Kamen said in his presentation….

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The POMS scores were overall significantly in favor of the exercise group, and the subscales all trended in favor of exercise, except for the anger subscale in which there was virtually no change, Kamen said.

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PEA Palmitoylethanolamide – “Glia & Mast Cells as Target, An Anti-Inflammatory & Neuroprotective Lipid Mediator”


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Another oustanding article on palmitoylethanolamide “PEA.” I have seen profound results with it relieving intractable neuropathic pain in a woman with CRPS for years, and I suspect it may help Major Depressive Disorder but that remains to be tested.

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I need to add that opioids create pain. One mechanism by which that occurs is that opioids create pro-inflammatory cytokines, which creates more pain. Patients may see no response to essential pain relieving medications untill they taper off all opioids and allow the system to stabilize. Otherwise, they will have pain forever and it may increase.

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Glia and mast cells as targets for palmitoylethanolamide,

an anti-inflammatory and neuroprotective lipid mediator

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Authors  Skaper SD, Facci L, Giusti P.

Mol Neurobiol. 2013 Oct;48(2):340-52.  Epub 2013 Jun 28.

Abstract

Glia are key players in a number of nervous system disorders. Besides releasing glial and neuronal signaling molecules directed to cellular homeostasis, glia respond also to pro-inflammatory signals released from immune-related cells, with the mast cell being of particular interest. A proposed mast cell-glia communication may open new perspectives for designing therapies to target neuroinflammation by differentially modulating activation of non-neuronal cells normally controlling neuronal sensitization-both peripherally and centrally. Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can be upregulated as a result of tissue damage or stimulation of inflammatory responses. Such molecules include the N-acylethanolamines, whose principal family members are the endocannabinoid N-arachidonoylethanolamine (anandamide), and its congeners N-stearoylethanolamine, N-oleoylethanolamine, and N-palmitoylethanolamine (PEA). A key role of PEA may be to maintain cellular homeostasis when faced with external stressors provoking, for example, inflammation: PEA is produced and hydrolyzed by microglia, it downmodulates mast cell activation, it increases in glutamate-treated neocortical neurons ex vivo and in injured cortex, and PEA levels increase in the spinal cord of mice with chronic relapsing experimental allergic encephalomyelitis. Applied exogenously, PEA has proven efficacious in mast cell-mediated experimental models of acute and neurogenic inflammation. This fatty acid amide possesses also neuroprotective effects, for example, in a model of spinal cord trauma, in a delayed post-glutamate paradigm of excitotoxic death, and against amyloid β-peptide-induced learning and memory impairment in mice. These actions may be mediated by PEA acting through “receptor pleiotropism,” i.e., both direct and indirect interactions of PEA with different receptor targets, e.g., cannabinoid CB2 and peroxisome proliferator-activated receptor-alpha.

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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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Palmitoylethanolamide (PEA) – Boosting Its Anti-inflammatory Immune Response


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Discovery could lead to new immune-response drugs for allergies, illnesses and injuries

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Improved spinal cord injury & inflammation in mice

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Medical news November 17, 2009, announced that “UC Irvine pharmacology researchers have discovered a way to boost levels of a natural body fat that helps decrease inflammation, pointing to possible new treatments for allergies, illnesses and injuries related to the immune system.”

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“For decades, it has been known that this fat, called palmitoylethanolamide (PEA), is a potent anti-inflammatory substance that reduces both allergic symptoms and occurrences of rheumatic fever, but researchers understood little about how PEA works.”

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I”n a study appearing online in the Proceedings of the National Academy of Sciences, Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences at UCI, and colleagues found that levels of PEA are tightly regulated by immune system cells. In turn, PEA helps control the activity of these cells, which are called into action to fight infection, disease and injury in the body.”

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They found a protein, an enzyme that breaks down molecules that control cell inflammation and deactivates PEA. They then created a novel compound that prevents the breakdown.

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“When given to rodents, the compound increased the levels of PEA in their immune cells and reduced the amount of inflammation elicited by an inflammatory substance. Furthermore, when administered to the spinal cords of mice after spinal cord injury, the compound decreased inflammation associated with the trauma and improved the recovery of motor function.”

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UCI is collaborating with the Italian Institute of Technology in Genoa to develop a range of immune-response drugs. 

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Source: University of California – Irvine

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Refer an earlier post on PEA here.

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Palmitoylethanolamide is sold as PeaPure, a food supplement, available from the Netherlands and imported by a local pharmacy here. I have submitted a paper for publication on the treatment of vulvodynia and proctodynia with PeaPure and a topical cream. That source will be posted once it is accepted.

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I have been seeing some exciting responses to treatment of intractable pain with PeaPure. I invite others who use it to add comments below so that we may all learn from your experience.

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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.

.

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.

~~~~~

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.

.

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

.

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Complex Regional Pain Syndrome – Review of Inflammation & Meta-analysis


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Neurology, the journal of the Academy of Neurology, has published “Inflammation in Complex Regional Pain Syndrome, a systematic review and meta-analysis” on July 1, 2013.

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The study was supported by grants from the Australian National Health and Medical Research Council, the Canadian Institute of Health Research, the Dutch consortium on CRPS and the Dutch Ministry of Economic Affairs.

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They found “a proinflammatory state in blood, blister fluid, and CSF.” Profiles differed in acute and chronic cases.

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Levels of neuropeptides in blood and blister fluids were not higher in CRPS than in controls.

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The inflammatory profile reflected a generic chronic pain state. There was no signature specific to CRPS. Chronic pain is associated with higher levels of proinflammatory activity.

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Acute cases did differ from chronic. But affected limbs did not show higher levels of inflammation than limbs that were not affected.

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Of interest, they found significant variability in concentrations of inflammatory factors which may suggest the data reflects methodological errors. Or it may suggest that CRPS is not a distinct disorder but is a collection of disorders that appear similar clinically, or the inflammatory response is not consistent, or that important clinical subgroups exist, for example hot vs cold CRPS or variations that present with significant autonomic disorders or systemic involvement.

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They noted a recent review of treatments that found little evidence that prednisolone improves symptoms of CRPS. And they note conflicting evidence for free-radical scavengers (dimethyl sulfoxide and N-acetylcysteine). They point out the latter trials were small and of mixed quality, however I have personally seen patients who respond to those treatments.

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They recommended formal, large, high quality studies to assess the efficacy of cytokine inhibitors (TNFα inhibitors) or immunosuppressive medication. They recommended more in vivo work on the immunomodulatory effects of analgesic medications such as morphine that has, in vitro, been shown to decrease the anti-inflammatory cytokine IL-10 and increase the proinflammatory IL-12 thus predisposing to more pain.

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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.

.

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

.

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