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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For My Home Page, click here:  

Welcome to my Weblog on Pain Management!

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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:  

Welcome to my Weblog on Pain Management!

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Opioids increase risk of chronic pain – potentiate pain – faster, stronger, longer. Activate TLR4 receptor on microglia, blocked by low dose naltrexone (LDN)

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Professor Linda Watkins was the distinguished keynote speaker at the May 2015 American Pain Society annual meeting and gave the NIH 2015 Kreshover Lecture:

“Targeting Glia to Treat Chronic Pain: Moving from Concept to Clinical Trials.”

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The University of Colorado at Boulder describes her work: 

She has authored or co-authored over 190 book chapters, review articles and journal articles.

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Dr. Watkins’ research focuses on 3 inter-related areas. Her primary research interest is understanding how to control clinically relevant pathological pain states. Her group’s research points to a novel reason that clinical pain has been impossible to successfully control. That is, pathological pain is being created and maintained by a surprising cell type, namely glia. These cells, upon activation, dysregulate normal pain processing by the spinal cord neurons.

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Medical News Today published news of her recent study April 19, 2018

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“Opioids may increase risk of chronic pain.” They potentiate pain “faster, stronger, longer” and activate the TLR4 receptor on microglia. That receptor is blocked by low dose naltrexone (LDN).

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Opioids trigger inflammation in the brain and spinal cord. This is an elegant study by renowned Prof. Linda Watkins at the University of Colorado Boulder, with Peter Grace. His early work on LDN brought him from Australia to postdoc at her lab and now research at MD Anderson Cancer Center.

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“Having been used in one form or another for millennia, opioids beat pain into submission, quickly making the patient more comfortable. The latest study, which was carried out at the University of Colorado Boulder, turns this firmly held notion on its head.

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Senior author Prof. Linda Watkins, from the Department of Psychology and Neuroscience, says, ominously, “[…] there is another dark side of opiates that many people don’t suspect.”

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In this case, it is not addiciton issues that Prof. Watkins is referring to. Paradoxically, opioids may actually prolong pain following surgery. The results were published recently in the journal Anesthesia and Analgesia.

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Postsurgical pain and opioids examined

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For the study, Prof. Watkins and colleague Peter Grace, of MD Anderson Cancer Center in Houston, TX, carried out laparotomies on male mice. This procedure involves making an incision through the abdominal wall to access the interior of the abdomen, and it is done on tens of thousands of U.S. individuals each year.

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“Opiates are really effective for acute pain relief. There is no drug that works better. But very little research has been done to look at what it is doing in the weeks to months after it’s withdrawn.”

Peter Grace

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Following surgery, one group of rats received the equivalent of a moderate dose of morphine for the next 7 days, while another group received morphine for 8 days, and the dosage was tapered off by day 10.

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Another group was given morphine for 10 days, after which point treatment stopped abruptly. A final group was given saline injections rather than morphine as a control.

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And, in another experiment, a group of rats received a 7-day course of morphine that ended 1 week before surgery was carried out.

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Before the morphine regimes commenced, and after they had been completed, the rats’ sensitivity to touch was measured, as was the activity of genes related to inflammation in the spinal cord.

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Compared with rats given saline, those that received morphine endured postoperative pain for over 3 additional weeks. Also, the longer the morphine was provided, the longer the rats’ pain lasted.

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The study also revealed that tapering of morphine dosage makes no difference. As Grace explains, “This tells us that this is not a phenomenon related to opioid withdrawal, which we know can cause pain. Something else is going on here.”

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How can morphine raise postoperative pain?

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The next question to ask, of course, is what drives this counterintuitive effect. Prof. Watkins calls it the result of a “one-two hit” on glial cells.

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In the brain, glial cells are more numerous than neurons. They protect and support nerve cells and, as part of their role as protector, they direct the brain’s immune response, including inflammation.

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The first “hit” occurs when surgery activates glial cells’ toll-like receptor 4 (TLR4). Prof. Watkins calls these “not me, not right, not O.K.” receptors; they help to orchestrate the inflammatory response. This first hit primes them for action when the second hit occurs.

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The second hit is morphine, which also stimulates TLR4. As Prof. Watkins explains:

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“With that second hit, the primed glial cells respond faster, stronger, and longer than before, creating a much more enduring state of inflammation and sometimes local tissue damage.”

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Although the study is in an animal model and will need replicating in humans, it does line up with previous findings.

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For instance, in 2016, the same scientists published another animal study, which found that a few days of opiate treatment for peripheral nerve pain exacerbated and prolonged pain. In that study, the activation of inflammatory pathways was also implicated.

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“An unusually high number of people end up with postoperative chronic pain,” explains Prof. Watkins. In fact, millions of U.S. individualssuffer with chronic pain. “This new study lends insight into one explanation for that.”

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Interestingly, the rats that received a course of morphine that ended a week before surgery did not experience prolonged postsurgical pain, leading the study authors to conclude that there is “a critical window for morphine potentiation of pain.”

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Because opioids are currently considered the best course of action to deal with postoperative pain, if these results are replicated in humans, it leaves medical science in a difficult situation.

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This is why Prof. Watkins is focusing much of her energy on designing drugs that could be given alongside opioids to dampen down the inflammatory response. She is also exploring alternative painkillers, such as cannabinoids.”

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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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Please IGNORE THE ADS BELOW. They are not from me.

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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.

• According to the World Health Organization (WHO; 2010), major depression also carries the heaviest burden of disability among mental and behavioral disorders. Specifically, major depression accounts for:

  • 3.7% of all U.S. disability-adjusted life years (DALYs); and,

  • 8.3% of all U.S. years lived with disability (YLDs).

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• 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.

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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.

~~~~~

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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Cannabis: CBD may help pain when rectal suppository morphine is a problem

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Marijuana, cannabis, is overlooked for pain control

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CBD – cannabidiol — is the immune/glial suppressor

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It is anti-inflammatory in brain and spinal cord

 

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Correction 3/28/16:

It is not legal to transport CBD to states where marijuana is illegal, though it has no psychoactive properties. This is explained in detail by two doctors who wrote in drugpolicy.org, March 2015. I recommend reading the article as it makes several important points.

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The cannabis plant, and everything in it, is illegal under federal law. And even in states where it is legal, it is not legal to ship cannabis products from state to state, or to leave the state with such a product.

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A recent study from Israel showed that CBD in its natural form as a whole plant extract is superior over a single, synthetic CBD compound for treating illness. The plant has continually outperformed synthetic versions in research studies.

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…There are many support groups for children with epilepsy whose parents are using medical cannabis, such as this forum run through the Epilepsy Foundation. Connecting with them can be a great resource for staying on top of the developments with CBD and the other therapeutic cannabinoids in the cannabis plant.

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Dr. Malik Burnett is a former surgeon and physician advocate. He also served as executive director of a medical marijuana nonprofit organization. Amanda Reiman, PhD, holds a doctorate in Social Welfare and teaches classes on drug policy at the University of California-Berkeley.

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Cannabis has been used for thousands of years. It has been in the U.S. pharmacopoeia since 1850. A medical textbook from the 1920’s lists medical uses for cannabis. A Mexican American grandfather on hospice in 1995, explained how cannabis had helped his arthritic joints decades before.

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When alcohol prohibition failed and was repealed in 1933, Harry J. Anslinger, head of the Federal Bureau of Narcotics from 1930 to 1962, created the word marihuana claiming it led to addiction, violence, overdosage. Anslinger used racist propaganda to instill fear in Americans that only Mexicans and Negros use cannabis which led to creation of the Marijuana Tax Act passed by congress in 1937. Not unlike the CDC Opioid Guideliness of March 2016, it was passed over the objections of the AMA.

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The American Medical Association (AMA) opposed the act because the tax was imposed on physicians prescribing cannabis, retail pharmacists selling cannabis, and medical cannabis cultivation/manufacturing. The AMA proposed that cannabis instead be added to the Harrison Narcotics Tax Act. The bill was passed over the last-minute objections of the American Medical Association. Dr. William Creighton Woodward, legislative counsel for the AMA objected to the bill on the grounds that the bill had been prepared in secret without giving proper time to prepare their opposition to the bill. He doubted their claims about marijuana addiction, violence, and overdosage; he further asserted that because the word Marijuana was largely unknown at the time, the medical profession did not realize they were losing cannabis. “Marijuana is not the correct term… Yet the burden of this bill is placed heavily on the doctors and pharmacists of this country.”

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Israel’s Professor Rafael Mechoulam is widely recognized for his work on cannabis over more than 40 years. He and his lab isolated and identified THC, CBD, cannabinoid receptors, endogenous cannabinoids – your brain makes two of them! Your body has more cannabinoid receptors than any other type. It was he who published 40 years ago that CBD controls certain types of epilepsy in children – and it was ignored until Dr. Sanjay Gupta publicized this in the last one or two years.

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Professor Mechoulam says CBD from the plant (the plant is illegal in the United States) outperforms synthetic CBD.

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However, standards for CBD products do not exist, assays may be unreliable, it may be extracted with harsh chemicals that are harmful to those who are ill, and FDA has warned against false claims of efficacy. 

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Nevertheless, there are indications CBD may help pain. It has no psychoactive properties. It does not cause intoxication. There is no THC in it.

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CBD, Cannabidiol, is one of the 86 known cannabinoids in the cannabis plant that has 400 chemicals. In addition, the plant has perhaps 100 or 200 unique terpenes, also said to help symptoms. 

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Topical CBD may help – keep that in mind when Blue Shield’s formulary offers only rectal suppository morphine (unless you wait days and hope they will approve a prior authorization).

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I received a note today about Colorado Hemp Farmers:

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a woman in her sixties suffering from sciatica who is having her nurse rub her back with a coconut oil extract of a specific strain of industrial hemp rich in CBD, but without significant THC. She reports that the pain alleviation is remarkable with the soothing extract, which she judged to be superior to when commercially available CBD oil was used. 

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Have any readers have tried CBD for pain?

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Your feedback would help to inform researchers to add an additional arm to the tests now being done in rats.

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I have heard from one man with severe pain today. He uses CBD in many forms. It helps pain a little, and also it is calming. He describes it like you know pain is better after you take ibuprofen. Similar with CBD. He does not feel at all drugged.

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This site is not for email.

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

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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.

~~~~~

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 educational website is

NOT advocated by me and NOT approved 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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Opioids Kill White Americans – Is it opioids or suicide or addiction or untreated pain?

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“Drug Overdoses Propel Rise in

Mortality Rates of Young Whites“

New York Times

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Yes, white Americans, headlined yesterday by Gina Kolata and Sarah Cohen, New York Times science writers.  This article points to the highest mortality in young whites. See post early November on the Princeton researchers who reported deaths in white Americans. True, infants and children have severe pain, but this new article is on young white adults.

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Those who are anti-opioid and those who lost a loved one from opioids and heroin (an opioid that helps pain), will send in comments to the paper so that everyone can see how bad opioids are. Most patients who take opioids are too disabled from pain to write.

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Pain is stigmatized, opioids stigmatized, people in pain are stigmatized, doctors who treat pain are stigmatized. Any wonder 97% of medical schools do not teach pain management?

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Is it opioids or suicide or addiction or untreated pain that is killing our youth?

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How many suicides have opioids prevented? Americans make up less than 5% of the global population but consume 80% of the world’s supply of opioid prescription pills. What if your cancer pain now becomes severe intractable chronic pain? Cancer has been changing. The survival rate has increased, and many of these cancer patients treated with opioid therapy, survived the cancer but have residual chronic pain from cancer or its treatment. Surely they are among the 18,000 white people who died.

 

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Please read the earlier post this week on the ethics of opioid treatment, on

CDC’s imminent radical cut in opioid doses for 100 million patients nationwide.

Use search function above photo – type in CDC or DEA.

Your pain. Your lives. Their profit.

A thorny problem.

Tell us what happened to you. Doctors, tell us what you are seeing.

Have you been denied disability due to pain? Denied non-opioid treatment?

Chronic severe pain affects forty million Americans.

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Some insurers have denied or limited non-opioid treatments yet continued expensive opioids for decades. Has your insurance refused your treatment? Pain specialists have been barraged by denials for years.  Please comment below.

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As noted last week, I have spent 15 years developing alternatives to failed opioid treatment for chronic intractable pain and writing about that on these pages since April 2009. But opioids must be available as last resort.

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FACT:

• Opioids killed almost 18,000 Americans in 2014 – prescription opioids, not street drugs.

• 40 million American millions with severe pain, millions not thousands

• 100 million with chronic pain.

• CDC will imminently, radically cut everyone’s opioid dose

• Health insurers will oblige, and incidentally show increased profit to shareholders

• Suicide increases with untreated pain

• Death rates for “whites ages 25 to 34 was five times its level in 1999”

• This age group has more injuries from work and play that can lead to disability, job loss

• Insurance is unaffordable or not purchased by many young adults

• My own colleagues cannot afford high deductibles – prescriptions are now counted in deductibles, now unaffordable

• Can you afford $20,000 per month for your opioid or is cheap heroin more affordable? Can you afford your usual drugs on Medicare once you are in the “donut hole.” Can you afford $28 per day, $840 per month for gout, when colchicine was 12 cents a day a couple years ago?
  

  • Do insurance denials increase liklihood of cheaper alternatives such as heroin or illegal marijuana resulting in death by drug dealer?

  • Do exhorbitant costs of opioids lead insurers to deny your medication?

• Insurers have refused to pay for abuse-deterrent and tamper-resistant formulations of opioids

•  Insurers have refused to pay for proven, widely accepted, nonopioid analgesics:

  • Lyrica

  • Horizant

  • Gralise

  • Cymbalta

  • Does it help the DEA and NIH and universities to teach those as nonopioid alternatives when they are not covered and not affordable the rest of your life?

  • Insurers deny every known compounded analgesic though low cost and effective, even for Tricare’s disabled veterans, even 5% lidocaine ointment for nerve pain, dextromethorphan, oxytocin, low dose naltrexone – Stanford published research on naltrexone years ago and now doing research on it again for CRPS, many many others

  • Insurers deny proven analgesics that are used by armed forces, university hospitals, select doctors, for life threatening pain: ketamine
    

  • Insurers deny off-label analgesics that may work better than opioids, e.g. memantine, an Alzheimers drug – can relieve intractable nerve pain (French publication on CRPS/RSD pain)
    

  • Insurers deny medications that reduce side effects of opioids, e.g. nonaddicting modafinil popular with students, to increase alertness when opioids cause drowsiness that may cause injury, death – gosh 10 years ago!

  • Is drowsiness the cause of some of those 18,000 opioid deaths?
    

• Health insurers have refused coverage for treatments such as P.T., psychotherapy for coping skills, blocks.
  

• Insurers deny medications that relieve the withering side effects of opioid withdrawal, making it impossible for many to taper off, e.g. Adderall, Wellbutrin (dopamine)
  

• Cannabis, a nonopioid, classified by US Congress as Schedule I, illegal federally for human use, illegal to take on a plane or cross state/national borders, found on meteorites, made by sponges and some of the earliest living species on the planet, used for thousands of years for pain, while cocaine and methamphetamine are classified as Schedule II for prescription purposes.
  

• Opioids, even vicodin, require monthly doctor visits, costs, monthly for sixty years

• Why whites dying of opioids? People of color are denied prescription opioids. Stark data published for decades.

• Heroin is an opioid, cheap and available; its “unAmerican” – used in England for pain, used thousands of years for pain

• Untreated pain is one reason people turn to heroin, affordable is another

• Violence and drinking and taking drugs can begin with chronic pain and job loss, not always the other way around, chicken egg

• Opioids cost pennies to make, patient’s cost is $20,000 per month for Rx. Insurers paid what the market would bear… in the old days. Who is trapped in the middle of this fight for shareholder profit?
  

  • How many of us would take 2 or 4 extra pain pills when pain spikes to extreme for days?

  • If you are disabled, can you afford insurance or expensive prescription drugs?

• “Poverty and stress, for example, are risk factors for misuse of prescription narcotics,” Dr. Hayward said.

• When you are not getting enough sleep and rest, working too many hours overtime or 3 jobs, inflammation and pain spikes

• Misuse of opioids in > 33% (perhaps 48%?) of cancer patients at Memorial Sloan Kettering Cancer Center in high resource settings when insurance was better, published 1990’s.

• Cancer pain – usually time limited. Intractable chronic pain – forever.
  .How many jobs will be lost and how many suicides when CDC imminently imposes strict cuts in opioids?

•  DEA recently requires every pain patient taking opioids, including those with cancer, to be diagnosed “Opioid Dependent” — not only addicts – the same diagnosis for pain patients includes addicts. The term “addiction” has been equated to dependence by most psychiatrist over the past 30 years. It may be interesting to see what criteria are used to define “addiction” if any, in DSM V. Some important members acknowledge that the addition of dependence into addiction in DSM-III was a mistake….the DSM-V criteria will get rid of “abuse”, and will include craving. it will also apparently eliminate the legal/criminal criteria. DSM comments are extracted from here, with many good arguments on this epidemic, such as: “The US is leading the way in eradicating pain, but in doing so has created an unwanted byproduct: painkiller addiction.”
  .

  What would you want if you had intense chronic pain?

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  “For too many, and especially for too many women,” she said, “they are not in stable relationships, they don’t have jobs, they have children they can’t feed and clothe, and they have no support network.”

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  “It’s not medical care, it’s life,” she said. “There are people whose lives are so hard they break.”

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Opioids kill – or is it untreated pain?

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Pain kills, a maleficent force.

No one can help you. Only you have the tools to do it

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Alarms went off for me on radical opioid cuts in October and I posted when

DEA suddenly held conferences across the nation on sharply cutting opioid doses.

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How many of us especially seniors and male persons refuse to learn or use coping skills that

reduce pain without medication?

How many of us refuse to diet and lose weight to reduce pain and/or disability?

Politicians are sued if they tax sales of sugar loaded soft drinks.

One single can of soda per day exceeds acceptable sugar limits for entire day.

Snacks need to say much much time it takes to burn off fat –

quarter of large pizza 449 calories, walk off 1 hr 23 min;

large coke 140 calories, walk off 30 minutes.

Foods can be anti-inflammatory or pro-inflammatory.

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Obesity is pro-inflammatory.

So is lack of sleep.

People who sleep with animals in their bed and their bedroom, I’m talking to you.

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Yes, pain is in your mind.

Chronic back pain is no longer in the back, it’s in the brain, the pain matrix.

It’s behavior, not just pills. Pain is an emotional and psychosocial  and spiritual experience.

Work on it! Constantly.

Lord forbid we should teach stress reduction and meditation in grade school

and improve school lunches before kids start looking for heroin for pain.

Yes, kids have chronic pain, are sleep deprived, often obese.

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Isn’t this all un-American?

Injuries, pain, habits, pace activities, learn to avoid and treat pain – start young.

Taxpayers end up paying for ignorance and disability.

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I will soon be posting published research that documents health insurers have refused to pay for nonopioid treatment and how health care policy aimed at all people with chronic pain leads to suicide when drastic cuts are made to opioid doses – Washington State we are looking at you. Florida you’ve made headlines and 60 Minutes TV specials years ago.

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Do please comment below if your health insurer has refused medication, physical therapy, psycho-therapy, cognitive behavioral therapy, stress reduction, for chronic pain.

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How many of you have been denied social security disability by doctors who don’t know how to diagnose RSD, Complex Regional Pain Syndrome? Let me know. I will pass on that data to researchers collecting information on untreated pain.

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I have written many times on these pages, and more often than ever these past years as insurers cut back more and more. This will rapidly get worse. We need your data.

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Please send in your stories. You are not alone.

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So many issues. Steven Passik, PhD, was interview by Lynn Webster, MD – emphasis in bold is mine. Dr. Passik pioneered in management of chronic pain and pain in addicts. He has read some of Dr. Webster’s book. “You’re calling, the need for love and connection and all those things in the book, I’ve been – what’s largely lacking is outright, at times animosity towards people with pain and I think there’s a lot of projections sometimes because the therapy – the stigmatized disease – treated in stigmatized people with stigmatized drugs and interventions and so, it’s like a hat trick of stigma.  I’ve been to my share of pain conferences lately that people are really talking about, “Okay, well there’s come a realization that opioid-only, drug-only therapy, is really not going to work to the best majority of this population.  It doesn’t [mean] that opioids should be ignored and we’ll get into that later, but that they’re going to work in isolation and should never been expected to.  And then they start advocating things that are a lot like supportive and cognitive behavioral therapy and to be practiced basically by the primary care physician or the pain doctor.  And the idea that, to me that’s in a way comical because as a psychologist myself, we’re dealing with the system wherein cognitive behavioral therapists can’t even get paid to do cognitive behavioral therapy.  And so, I think something’s got to give, and I think one of the main obstacle is that – and this really gets into the next question as well but I’ll come back to that more specifically – but when people have a set of whatever chronic condition that involves psychiatric motivational, lifestyle, spiritual as well as nociceptive elements, and we put a premium only on what you do to people, prescribed to people, put in people, take out of people, and then that’s only going to relegate the other kinds of treatment or the other kinds of ways in which a caring physician and treatment team would spend time with the patient to the very poorly reimbursed category.  You’ll always going to have a problem with people being treated with the kind of respect that should go along with treating that kind of an illness and it’s not unique even to chronic pain.  I’ve seen treatment scenarios with people who are taking care of people with pancreatic cancer, have an afternoon clinic that has 45 people in it.  I mean how you – something’s got to give in our healthcare systems and I do think that patients are going to have to stand up and say, “I don’t want to be on a conveyor belt.  I want to spend some time and make a connection with the people that are taking care of me and it’s not just about the piece paper in my hands, for a prescription or that I walk out the door with.”

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 The New York Times article further says:

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…This is the smallest proportional and absolute gap in mortality between blacks and whites at these ages for more than a century,” Dr. Skinner said. If the past decade’s trends continue, even without any further progress in AIDS mortality, rates for blacks and whites will be equal in nine years, he said….

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…Not many young people die of any cause. In 2014, there were about 29,000 deaths out of a population of about 25 million whites in the 25-to-34 age group. That number had steadily increased since 2004, rising by about 5,500 — about 24 percent — while the population of the group as a whole rose only 5 percent. In 2004, there were 2,888 deaths from overdoses in that group; in 2014, the number totaled 7,558….

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…For young non-Hispanic whites, the death rate from accidental poisoning — which is mostly drug overdoses — rose to 30 per 100,000 from six over the years 1999 to 2014, and the suicide rate rose to 19.5 per 100,000 from 15, the Times analysis found….

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…For non-Hispanic whites ages 35 to 44, the accidental poisoning rate rose to 29.9 from 9.6 in that period. And for non-Hispanic whites ages 45 to 54 — the group studied by Dr. Case and Dr. Deaton — the poisoning rate rose to 29.9 per 100,000 from 6.7 and the suicide rate rose to 26 per 100,000 from 16, the Times analysis found….

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…Eileen Crimmins, a professor of gerontology at the University of Southern California, said the causes of death in these younger people were largely social — “violence and drinking and taking drugs.” Her research shows that social problems are concentrated in the lower education group.

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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.

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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!

 

 

 

 

Side Effects of Neridronic Acid – Neridronate

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Neridronate

Neridronic acid

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This is a long response to detailed comments from Julie who had a reaction to the neridronic acid protocol for CRPS.

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The clinical trial on neridronic acid is extremely important and unique. It is important because it does not just cover symptoms, it actually may put CRPS into remission.

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If I had CRPS, I would not hesitate to accept short term side effects if I thought I could get long term benefit, even possibly remission. We need this study. It will not be available for anyone unless many enroll in the double blind study and hopefully soon so that results can be submitted to the FDA for approval.

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Please read her comments first, at the end of my post. And then my comments below.

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And because neridronic acid relates to bone metabolism, much later I will mention an area of research that is likely to be be valuable because it is the largest receptor system in the body, the endocannabinoid receptor system, the body’s own cannabinoid system.  Two ideas from Raphael Mechoulam, professor of Medicinal Chemistry at the Hebrew University of Jerusalem in Israel are keenly interesting:

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The Skeletal Endocannabinoid System

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The Entourage Effect

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Glia make one of the cannabinoids in the brain, and glial research is where I suspect some of the best research will come

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Hopefully these ideas will stimulate  research.

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In response to Julie, I wrote:

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Julie, I am so sorry to hear of the difficulty you had to go through for such a long time. And relieved that you got through it. I and, I’m sure everyone else, thanks you for volunteering. We will all benefit. And we all hope that if any reaction is to occur, please let it be rare. It appears that yours is rare.

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I know everyone is with you, and we bring all our hopes for the unknown. No one has the answer of what to do with intractable pain of any kind, not just CRPS pain. We must, MUST, begin to do more research on intractable pain in humans. Neridronic acid is an important beginning to look at a new mechanism.

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CRPS has, in some people, escaped every known rational approach to treatment. Neridronate may be the best thing we can get. It takes time to learn how new medications work, and they have chosen wisely, I am sure.

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Be assured, I think good minds are working on the best. But it is unknown territory.  Numbers are needed – CRPS can be very dynamic. Flares and remissions wax and wane, so long term study must be done.

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We all see patients after CRPS flares and there is nothing more to offer. Not one thing. We urgently need something that works. We are hoping neridronic acid will be that rescue.

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Will remission last 12 months or 3 months or less?

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What are long term risks?

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How often could it potentially be given, or will remission really last for years in some? We all need to see numbers.

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Huge hopes are on this drug.

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We must balance hopes and fears.

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We recognize it is a new drug for a new purpose. We hope this research will drive many more studies on CRPS and/or intractable pain.

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Julie, thank you for allowing others to see details. It may help other volunteers to set aside time to recover any post infusion effects, if needed. Hope for the best, plan for the worst is the saying.

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No one yet knows how good the potential is for duration of effect. Remission could potentially be total, in some. How many?

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We are all learning how to treat chronic intractable pain.

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Skeletal Endocannabinoid System

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The highly decorated scientist who discovered THC and the body’s endocannabinoid system, Raphael Mechoulam, professor of Medicinal Chemistry at the Hebrew University of Jerusalem, recently mentioned the SKELETAL CANNABINOID SYSTEM in a 2014 documentary on his discoveries.

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The cannabinoid system interacts powerfully with the immune system in ways not yet studied. Why does your CRPS immune system affect the skeletal system and create pain?

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Cannabinoids are anti-inflammatory, analgesic, healing. The body makes its own. We need to study the biggest receptor system in the body. It is a gaping hole that is left out of existing work on the immune system.

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And how much are glia and our innate immune system in CNS— how much are they studied?

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Please let there somehow be funding for many studies on humans – but let’s begin one study, guided by Distinguished Professor Linda Watkin’s lab. She is the only scientist who is doing translational work from  basic research in the lab to humans.

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Professor Watkins has the best clinical solution I have seen: IL-10 has remarkable potential to bring your pain to zero for 3 months or more at a times. Your brain makes it. It is *the* anti-inflammatory cytokine. Her lab has been the world leader in glial research. Where is the funding for what may be the most important area of work for intractable mood disorders and treatment resistant depression?

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Glia

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How do hundreds of now usable drugs create pro-inflammatory cytokines thus make more pain or more major mood disorder?

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And which of these hundreds of drugs on our formulary reduce inflammatory cytokines?

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What is the role, if any, of some of the medications used by rheumatologists to dampen the hyperactive immune system in autoimmune disease? Risks, but possible gain. We will never have all the answers. ALL the answers for everyone is hard to imagine.

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How do hundreds of existing drugs affect the balance of CNS cytokines?

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Skeletal Endocannabinoid System – see Raphael Machoulam’s lab in Israel. May be critical for CRPS and for osteoporosis in seniors.

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Mechoulam’s lab would bite at the chance to get funded to work with the Italian and USA CRPS study.

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Julie — I am heartened that you may be able to see Professor Ott who may be one of the foremost researchers on bone metabolism if not number one.

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I posted three times on bisphosphonates last year and hope they are a good review for others.

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The Entourage Effect

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Mechoulam also has an important concept that probably applies to my method of trying to modulate these powerful intractable pain syndromes.

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Simple concept – brilliant:

The Entourage Effect. Drugs are like politicians. A famous politician may walk unrecognized, but when you surround him or her with many people, even of lesser status, the politician has a far more powerful effect.

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I don’t know how you guys do it.

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Respectful best wishes.

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I know some of you ignore this, but I have to repeat:

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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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This material 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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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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Low dose naltrexone (LDN), novel anti-inflammatory treatment for chronic pain

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A review of the clinical use of low dose naltrexone appeared today by Younger, et al. from Stanford (see e-Pub below).

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Naltrexone is one of the most important medications I have prescribed, alone or in combination with other medications for intractable chronic pain and/or treatment resistant Major Depressive Disorder or Bipolar Disorder. It has been most extensively used anecdotally and off label since 1985 for treatment of Multiple Sclerosis.

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Naltrexone acts on two receptors in the central nervous system: (1) the opioid receptor and (2) the TLR4 receptor on glia.

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(1) The opioid receptor is blocked by naltrexone. Naltrexone cannot be given to someone who uses opioid analgesics because it would cause a severe or unpleasant opioid withdrawal reaction. But in low dose, it can do better than opioids for relief of intractable pain. I would like to see it tried for pain, alone or in combination, before any opioid is started. And if on opioids, taper slowly off opioid in order to see how superior low dose naltrexone is. See case reports elsewhere on this site.

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Low dose naltrexone is quite different than its use in high dose where it is FDA approved for addiction to alcohol and opiates. Naltrexone reduces craving. However, in high dose, it blocks the endorphins, the opiates that your brain produces, thus causing pain and depression.

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(2) The TLR4 receptor was discovered by Bruce Beutler, MD, working at Scripps Research Institute. He won the Nobel Prize in 2011 for that profound work. The TLR4 receptor is found on the microglial cell in the central nervous system. The microglia far outnumber nerve cells in the brain and spinal cord. I discussed a small portion of the vast science of the importance of glia, your innate immune system and inflammatory cytokines, here. This research on glia, the innate immune system, is new, largely in the last 10 to 15 years.

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One of the mechanisms by which opioids create pain is that opioids trigger glia to release pro-inflammatory cytokines, i.e. opioids create a neuroinflammatory response in a manner similar to endotoxin from bacteria. Opioids upset the balance of pro- and anti-inflammatory cytokines to create more pain. Naltrexone does the opposite by its action on the glial TLR4 receptor reducing pro-inflammatory cytokines and relieving pain.

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Inflammation kills! Glia and/or the inflammation produced by glia are involved in many pathological processes: Alzheimer’s, Parkinsons, ALS, MS, chronic pain, depression, autoimmune disease, cancer, atherosclerosis. The TLR4 receptor is necessary for death or destruction of oligodendrocytes and myelin, as occurs in multiple sclerosis. Does that mean low dose naltrexone may play a role in modulating these conditions?

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See reviews by distinguished Professor Linda Watkins, PhD, and Mark Hutchinson, PhD, on glia, neuroinflammation and the neuroimmunopharmacology of opioids. Besides glia, Watkins and Hutchinson have recently discovered Toll-like expression of neuronal receptors in pain states.

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For access to articles on glia, cytokines and the TLR4 receptor, see the RSD Syndrome Association library of key publications. And donate to them. They have supported key research in pain when NIH gave less than half of 1% to pain research in 2006, now far less since the deadly the recession of 2008 and the ever threatened fight over funding the national debt.

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Being interested in glia, and treating so many patients with Major Depressive Disorder who had failed other treatments, I did a review of depression and glia and found the same increase in pro-inflammatory cytokines in depression that are found in chronic pain. Since low dose naltrexone is anti-inflammatory, i.e. it modulates or resets the balance of pro-inflammatory and anti-inflammatory cytokines that are produced by glia, I felt it important to try in Major Depressive Disorder. Besides, I had seen its profound effect on so many different forms of intractable pain for many years. Use of LDN has never been associated with toxicity and rarely any side effects.

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My patient had severe suicidal ideation with Major Depressive Disorder for more than three months, unchanged after treatment at a psychiatric center where she had stayed almost four weeks. She began with 4.5 mg in the office and 25 minutes later, on the drive home, her appetite returned! She walked in the house and her dad was astonished – she no longer walked like she was 105 years old! She had the energy to do her laundry and cook for the family for the first time in more than three months.

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Another person for whom I prescribe naltrexone for Major Depression, wrote to me saying Massachusetts General, a Harvard Hospital, was starting clinical trials of low dose naltrexone for Major Depressive Disorder. Other new clinical trials of low dose naltrexone can be found here.

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Jared Younger, PhD, from Stanford first published on the use of naltrexone in fibromyalgia – see my discussion here.

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Today in PubMed, ahead of print, Dr. Younger et al. publish a review of low dose naltrexone, a glial modulator.

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The use of low-dose naltrexone (LDN) as a novel

anti-inflammatory treatment for chronic pain

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Authors  Younger J, Parkitny L, McLain D.

Journal

Clin Rheumatol. 2014 Feb 15.  [Epub ahead of print]

Affiliation

Abstract

Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.

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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.

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

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

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

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

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

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Science Daily announcement:

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

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Lincoln University, UK, heralds this promising discovery:

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

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

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The molecule was able to alleviate hypersensitivity to inflammatory pain.

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

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

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~~~~~

The material on this site is for informational purposes only.

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

~~~~~

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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