A New Class of Pain Medicine from Cancer Cells – PD-L1 inhibits acute & chronic pain


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For the nonscientist, this report may explain better:

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Cancer actually yields a painkiller

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Scientists have discovered a potent painkiller in an unlikely place — cancer cells.

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This painkiller strongly inhibits acute and chronic pain in mouse models of melanoma, according to a study published Monday in Nature Neuroscience.

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Called PD-L1, the molecule is known to inhibit immune function, which helps cancers evade immune surveillance. It’s also produced in neurons. If it can be used to make an analgesic drug, it would represent a new class of painkillers, something badly needed.

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The molecule acts by targeting a cellular receptor called PD-1 and has been a longstanding target of cancer therapies called checkpoint inhibitors seeking to activate the immune system. But its painkilling effect is news.

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Ru Rong Ji of Duke University was senior author. Gang Chen and Yoang Ho Kim, also of Duke University, were first authors. The study can be found online at j.mp/cancerspain.

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…..Dr. Patel, oncologist from UCSD says: “This could result in a therapy that helps patients in a year or two years, just because so much has been done in the field.”

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The relationship between cancer and pain is complex, Patel said. PD-L1 suppresses inflammation, which activates the immune system, and also causes pain, Patel said. But there are other ways of activating the immune system, such as with the new cancer immunotherapy treatments, which don’t increase pain, he said.

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….The increased pain response is also caused by the cancer drug nivolumab. The drug, sold under the name Opdivo, targets PD-1 and shows success in treating melanomalymphoma and lung cancer. It produced strong allodynia for five hours in the mice, according to the study.

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Nivolumab is one of the new checkpoint inhibitor cancer drugs that targets PD-L1 receptors with immunomodulatory antibodies that are used to enhance the immune system. They can produce a wide spectrum of side effects termed immune-related adverse events (irAEs) with inflammation due to immune enhancement involving several organ systems.

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This is not my field and perhaps I am wrong. But if treating those cancers with immunotherapy causes the worst known neuropathic pain by blocking checkpoint inhibitors, is it possible that a new pain drug having the opposite mechanism could relieve pain but cause cancer?

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This Nature publication references the growing body of work from the lab of Linda Watkins, PhD, et al, published in 2014:

.Pathological pain and the neuroimmune interface

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Reciprocal signalling between immunocompetent cells in the central nervous system (CNS) has emerged as a key phenomenon underpinning pathological and chronic pain mechanisms. Neuronal excitability can be powerfully enhanced both by classical neurotransmitters derived from neurons, and by immune mediators released from CNS-resident microglia and astrocytes, and from infiltrating cells such as T cells.

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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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Cannabis risk, death from fungal infection, demanding peer reviewed science. Not even billions can buy CBD if it is classed as Schedule I


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“IMPROVING MICROBIAL DETECTION STANDARDS FOR CANNABIS”

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The full article in O’Shaunessy’s is recommended. I’ve extracted a few parts.

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“If the government is going to tax us, in return they’ve got to provide us with needed services. And that means well-equipped analytic test labs run by disinterested technicians.” [emphasis mine]

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“Let’s make measured changes before another patient is harmed while demanding peer reviewed science is used to guide the regulatory process. In an era of fake news, science by press release with “beliefs” derived from companies that have a vested interest in seeing more cannabis safety testing should be hyper scrutinized.”

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“I think the cannabis-testing labs should be operated by the Department of Public Health, overseen by Commissioner Raber (and equally proficient chemists in every city and state) and staffed by well trained and well paid technicians whose pensions are secure.”

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The importance is that many patients who are immunosuppressed use medical marijuana, and need to use it safely because nothing else helps as well, including those who are immunosuppressed and don’t know it. For example, many do not know that diabetics are immunosuppressed. Those with autoimmune diseases, chronic renal disease, may be using medical cannabis and should demand testing be done with their taxed dollars as should we all. This has been one of the most useful herbs in history, for thousands of years, and can give balm and relief even to shattered nerves, especially now that healthcare insurers are denying to pay for pharma’s gobsmacking overnight billious costs.

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gobsmacking billious costs

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getting up to speed on legal cannabis &

 research on endocannabinoid systems

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This is a timely issue. Discuss with your doctor, get your representatives to help to legalize it nationwide. It may be the only thing that can help, or the only one that doesn’t constipate or cause erectile dysfunction or interact with other drugs. We don’t want our medication infected, even if we want to use cannabis for relaxation and pleasure. The Xanax’s and Ativan’s could be improved upon if only the right science is funded.

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“On February 7, the Daily Mail reported a cancer patient in northern California died from a fungal infection that authorities suspect was caused by the inhalation of contaminated medical cannabis.”

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snip

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“Furthermore, molecular techniques can be used to assess whether this cancer patient’s infection was actually cannabis derived. This is possible by using PCR and sequencing as performed by Remington et al. on the cannabis material and on the patient to confirm such an event.”

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“Rather than jumping to conclusions from a news story about cannabis contamination (which may in fact be the case), officials should confirm, via molecular methods, that a fatal infection occurred from the consumption of contaminated Cannabis or from another source, such as a hospital acquired infection. Once confirmed, the scientific data can help drive the appropriate regulations forward to ensure patient safety.  Unfortunately, most regulations passed to date for microbial detection do not appropriately address patient safety and often suggest the use of antiquated, inaccurate technologies.  For instance, we have peer-reviewed evidence that the currently accepted 48-hour Petrifilm-based method currently in use fails to detect some of the most harmful microbes found on cannabis. The State of Colorado has recently come to similar conclusions and has moved their Petrifilm detection times from 48 hours to 60-72 hours while referencing a paper suggesting 120 hours may be required.  And even with these adjustments to the regulations, Petrifilms will never give as accurate results as PCR.” [emphasis mine]

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“All technologies used to ensure product quality and patient safety should be peer reviewed. DNA-based methods are imperative to patient safety, as they are accepted, peer reviewed, and have been used for decades in other industries for similar purposes.”

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Kits to perform qPCR-based microbial testing on cannabis are commercially available at medicinalgenomics.com. We hold the largest sequence database of microbes found on cannabis and have kits that perform these tests in hours as opposed to days.”
[emphasis mine]

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“The technology exists to ensure safer cannabis for patients. Let’s make measured changes before another patient is harmed while demanding peer reviewed science is used to guide the regulatory process. In an era of fake news, science by press release with “beliefs” derived from companies that have a vested interest in seeing more cannabis safety testing should be hyper scrutinized. This extends to our own work at Medicinal Genomics and underscores our publication history in this space.”

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snip

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O’Shaughnessy’s retro message:

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Medicinal Genomics’s qPCR technology is undoubtedly superior and would have picked up the aspergillus that may have been fatal to the California  patient. But how widespread is the danger, really? In San Francisco in the ’90s, many thousands of AIDS patients whose immune systems were beyond “compromised” smoked untested crude herb, and I only heard of one rumored instance in which aspergillus may have been involved in a death. Donald Abrams, MD, might be able to confirm or correct my reassuring recollection.”

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“That said, of course the labs testing cannabis should employ the best available technology. The question, is who should pick up the tab?” [emphasis mine]

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“When I was working for the San Francisco District Attorney in ’01 or ’02 I called on Josh Bamberger at the city health department on Grove Street and asked if their lab would take on the testing of cannabis being sold at dispensaries. He said he didn’t have the budget or the personnel.  In the years ahead I was surprised that nobody from the movement/industry ever made the demand —not even the request— that a government agency take responsibility for testing medical cannabis. No patient advocate declared, “If the government is going to tax us, in return they’ve got to provide us with needed services. And that means well-equipped analytic test labs run by disinterested technicians.” [emphasis mine]

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“All around the world, PRIVATIZATION is the overwhelming socioeconomic trend of our time.  The Power Elite have done such a thorough job of selling off the commons and undermining the public sector that everybody now simply assumes that for-profit labs can and should take on the responsibility of protecting public health. “

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“I think the cannabis-testing labs should be operated by the Department of Public Health, overseen by Commissioner Raber (and equally proficient chemists in every city and state) and staffed by well trained and well paid technicians whose pensions are secure. And while we’re at it, how about free public education and single-payer medical care?”

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I keep getting the suspicion billions are being funneled rapidly down new rabbit holes using fear to prevent science. We must be able to do more than just prescribe  opioids for severe pain. Opioids cause inflammation which causes more pain. Cannabis is anti-inflammatory, analgesic, etc etc etc, and not allowed in hospitals, SNFs, or in facilities that seniors can only dream of retiring to when they can no longer manage at home. We need medical better choices.

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Medicinal cannabis is a healing plant with cannabinoids like ones that your body makes that helps you feel healthy and somehow influences the immune system more than any other system, while also lifting mood. Wouldn’t it be nice to know? It has 400 chemicals, not just two synthetic ones pharma makes. An exciting new cosmos in the body’s realm of more than just neuroscience. We have more cannabinoid receptors than any other kind in our body. We need to learn.
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Stop this Schedule I nonsense. Legalize cannabis. Privatize and regulate it like big alcohol, but keep it apart from big pharma, and endow strong university ties. For pete’s sake, fund the research immediately. We need it. The immune system needs it. The pain matrix needs it. Why should we allow euthanasia when we can treat pain and symptoms. Grandmothers used to know how. We are living in the dark ages with cannabinoid systems science. It is in starving infancy, Israel’s Mechoulam lab pioneering this blossoming for decades.
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Don’t forget to tell your representatives that you hear you may benefit from medical marijuana. Cannabis, marijuana, just may help, as it helped so many little children having hundreds of seizures each day, helped by just one of the cannabinoids in the plant: CBD.  It has been reported to almost completely stop the hundreds of daily seizures in possibly 50% —wouldn’t it be important to do research on it?

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CBD  has no psychoactive power. There is no high, no hallucinations. It actually blocks the psychoactive power of THC. It should be legal. The plant should be legal. It helps many medical conditions. I have posted an astonishing case months ago 100% relief with CBD. Instead it, just the other day, CBD got clearly classified as Schedule I. This must go to the courts. This insanity about a healing plant can be sanely managed, just like alcohol is managed. Without privatized prison systems that waste taxpayer dollars.

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We see new funnels of big money going down the rabbit hole. The urgency to privatize. We have a lot of people who cannot afford the American medical system, cannot afford doctors, who may get some relief even as a muscle relaxant or for sleep or anxiety.

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How can anyone respect a legal system that does not even allow research on a healing plant so important to the immune system?

 

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No amount of billions can buy CBD if it is classed as Schedule I.

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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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PEA in US (palmitoylethanolamide), PeaPure in Netherlands – DO NOT BUY OTHER SOURCES


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PEA in US is palmitoylethanolamide from Vitalitus

PeaPure in  Netherlands

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DO NOT BUY OTHER SOURCES

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PEA is thankfully available in the US since Spring 2016 from ONE company: Vitalitus. It is a trusted source. Buy PEA only from Vitalitus in the US, others are fraudulent sources.

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I strongly recommend that you AVOID any product with a “PEA-type” name trying to sell elsewhere in the US or on the web.

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One such fraudulent source is a foreign entity pretending to be in the US, and they are now listing a US address on Brickell Avenue, Miami, FL 33131 United States. But that is a virtual office address which is still listed for rent at $60/month.

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It looks like they’ve morphed the website and their product label. Very professional looking but AVOID THEM LIKE POISON. They keep trying to post comments on my website. They may even be buying advertising on my free site – anyone can advertise but I do not endorse products with this one exception, PEA, because it is unique.

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I have also seen “PEA-type” powder available on the web. Do not buy powders claiming they are pure palmitoylethanolamide. They are not trustworthy sources.

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Make sure your PEA comes only from a trustworthy source. In the US, that is Vitalitus. PEA works on the innate immune system, mast cells, and much more. There are more than 400 scientific publications on palmitoylethanolamide since it was rediscovered by a Nobel Prize Winner in 1993. Vitalitus’ PEA capsules are 100% palmitoylethanolamide. Pain relief is one of its immune functions. Your body makes it, plants make it, it has no toxicity, but follow directions or capsules will not fully absorb.

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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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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.

 

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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PeaPure – Palmitoylethanolamide for Nerve Pain or Migraine


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PeaPure is a glial modulator. It is available in Italy and the Netherlands as a food supplement and has been studied in multicenter clinical trials in Europe for several years. It is well tolerated with no side effects and is very helpful for neuropathic pain, headache, and osteoarthritis. It is anti-inflammatory and neuroprotective.

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Because it inhibits astrocyte activation and the over-expression of pro-inflammatory molecules and signals, it is being investigated in Alzheimer’s Disease.

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The mechanism of action of PEA was discovered in 1993 by Nobel laureate Rita Levi-Montalcini in her work on nerve growth factors. She found it is involved in metabolism of mast cells and published a series of papers on its self-healing effect of the body in response to inflammation and pain. Two recent publications from Jan M Keppel Hesselink, MD, PhD, and his colleagues at the Institute for Neuropathic Pain, Amsterdam, The Netherlands, describe case reports, one of which is the case of a woman with CRPS.

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The purpose of this post is to clarify dosing of PeaPure and how to take it for a sudden flare of pain. My apologies for failing to recall the source of these instructions which I believe was from the manufacturer and from here and here. The latter includes an excellent review of its mechanism.

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Description of PeaPure® 400 mg capsules
PeaPure® is a food supplement based on a natural and fatty-acid like compound.
The substance palmitoylethanolamide (PEA) is a physiologically active molecule that the body produces naturally.
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What the user should know prior to ingestion:
•    There are no known significant side effects.
•    PeaPure® can be taken simultaneously with other medicine. In case of doubt, it is recommended to first consult your doctor or a pharmacist.
•    Use during pregnancy is NOT recommended.
•    PeaPure® does not contain sugar, yeast, allergens, sorbitol, magnesium stearate, povidone or other ingredients.

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Dosage and administration – please refer to the manufacturer.

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UPDATE SEPTEMBER 2014

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It is with a heavy heart that I report this news:

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Palmitoylethanolamide is

now available only from the Netherlands,

sold as PeaPure, a food supplement.

  It is no longer able to be imported by a pharmacy, but we are hoping

that may change if we can interest a supplement manufacturer to make it available for the US.

Patent rights, attorneys are far beyond the resources of my local pharmacy.

 

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I have published this year, 2014, on the treatment of

vulvodynia and proctodynia with PeaPure and a topical cream.

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There are no studies to show us how often it may relieve nerve pain, but it is astonishing when it works. No toxicity, no side effects. Your brain makes it, plants make it. There is a growing literature on it and I have posted on some of its mechanisms. And in particular, its Anti-inflammatory, Analgesic, Neuroprotective Mechanisms.

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The material on this site is for informational purposes only, and is not a substitute for

medical advice, diagnosis or treatment provided by a qualified health care provider.

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

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

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

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