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In this section English articles are published on neuropathy.

Low-grade inflammation in Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (ME/CFS); treatment by palmitoylethanolamide supplement

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a disorder difficult to understand for many, especially for doctors who too often think this disorder does not exist. Well it does! Modern neurobiological research clearly found new insights in the cause of this disease. New findings point out that inflammatory pathways and immunity derangements play an important role in the pathophysiology of Myalgic Encephalomyelitis […]

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Chronic prostatitis/chronic pelvic pain syndrome, neurologic inflammation and autoimmune disease and palmitoylethanolamide

In a recent review it was highlighted that symptoms of chronic prostatitis/CPPS appear to cluster into a group with primarily pelvic or localized disease,  as well as in a group with more systemic symptoms, such as generalized pain disorders. There seems to exist a cluster of chronic pain conditions related to chronic inflammation, and in this cluster we can […]

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Visceral pain: a forgotten topic

Prof. Fernando Cervero from Montreal, Canada discussed at the EFIC 2013 in Florence an underserved but very important topic: visceral pain. Visceral pain is very underserved, as patients visit often organ specialists not interested in pain itself, but directly focussing on the underlying illness. However, as visceral pain is a cinderella in the pain field, […]

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Visceral pain: basic mechanism and science

At the 2013 EFIC congress on pain in FLorence the Ulf Lindblom Special Lecture was dedicated to visceral pain, and presented by Prof. dr. F. Cervero from The Alan Edwards Centre for Research on Pain, McGill University, Montreal, QC, Canada. Cervero pointed out that visceral pain is a prominent symptom of many clinical conditions. Visceral […]

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Palmitoylethanolamide, PEA: key items presented

In the following sequence of presentations we bring to you the essence of knowledge around the body-own compound and supplement palmitoylethanolamide! We start with the general introduction, an overview of palmitoylethanolamide, an endogenous cellular protectant in plants, invertebrates, vertebrates and humans, tested extensively since 1970 and widely available as food supplement. Its main action is […]

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Neuropathic pain: microglia controls neuronal network excitability

Microglia-neuron interactions are leading to altered neural network excitability, the pathogenetic base of neuropathic pain. Modern research demonstrates that one of the key factors driving neurons nuts in neuropathic pain is the inflammatory compound ‘Brain-derived neurotrophic factor (BDNF)’, released by microglia. [1] Microglial BDNF plays a key role in controlling neuronal excitability by causing disinhibition. This […]

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Channelopathies: increasing understanding

Inherited mutaions of ion channels can affect central and peripheral nervous system. Most of these chanches in the fundtion of ionchannels influence the function of brain, spinal cord, peripheral nerves or muscles. The disturbances are not continous, but intermittent.

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KRN5500 Kirin Brewery and Massachusetts General Hospital, DARA Biosciences

KRN5500 Kirin Brewery and Massachusetts General Hospital, is licenced to DARA Biosciences, and currently in phase II for neuropathic pain. KRN5500 (6-[4-Deoxy-4-[(2E,4E)-tetradecadienoylglycyl]amino-L-glycero-ß-L-manno-heptopyranosyl]amino-9H-purine) has been targeted for specific indications: Neuropathic Pain in cancer patients, in particular, chemotherapy-induced peripheral neuropathy (CIPN). KRN5500 is a novel non-opioid analgesic agent, a semi-synthetic derivative of spicamycin.

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Tai Chi for neuropathy

There are scientific studies showing that Tai Chi prevents elderly people from falls. Thus, as balance and gait are impaired in neuropathic syndromes, it makes sense to try Tai Chi if suffering from mild neuropathy. Here a quotation from a recent (2010) article on Tai Chi in neuropathy:

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Chronic idiopathic polyneuropathy: tired and prone to falls

ciap-wankel-op-de-benen.jpg This patient, born in 1926, is a vital man, but due to CIAP he was falling frequently, and was very tired. One year after we started treating this all was very much reduced, more than 50%. Here his story:

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Retigabine (D-23129)

Retigabine, a anticonvulsant, known already sinds 1995, activates Kv7 (KCNQ/M) channels in the axonal/nodal membrane of peripheral myelinated axons. 

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Working on a cure for diabetic neuropathy: cooperation TRDX & Genesis Biopharma

SciMeDent Health, Corp. f/k/a Trend Exploration, Inc. ("TRDX") cooperates with Genesis Biopharma, Inc. to work on a new development of curing (sic!) diabetic painful neuropathy. With nearly 300 million people suffering from diabetic neuropathy workld wide and only in de USA each year 80.000 amputations due to diabetes, there is a hugh unmet need in this indication.  

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Cannabis cookies for neuropathic pain

Cannabis treatment for meuropathic pain using low dose cannabis during prolonged periods of time due to slow resorption from butter rich cannabis cookies: a better way to administer cannabis than the classical joint or marihuana tea.

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Palmitoylethanolamide (PEA) versus NSAID in the treatment of TMJD pain

In a head to head comparison study the Italian research group from the Department of Orthodontics, of the  School of Dentistry, at the University of Bologna, could demonstrate that treatment with the natural analgesic compound palmitoylethalonamide (available under the brandnames een PEA-houdend product®  or PeaPure® ) was superior over the treatment with a classical NSAID in temporomandibular joint disorder (TMJD), or Costen syndrome.

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Gliopathic pain, asteropathic pain..


Glia and asterocytes play a central role in neuropathic pain, and gliopathic pain, or asteropathic pain will become new synonyms for neuropathic pain. In a recent hallmark paper the term ‘Gliopathic pain’ was coined.

This is a reason to put our magnifying glass on glia. Gliamodulating drugs will become a new class of neuropathic drugs, the so called gliopathic modulating drugs, and the first prototype, the endogenous fatty acid palmitoylethanolamide, has already been explored in positive proof of principle studies. 

For more than a century doctors are aware of the special properties of glia in response to injury. In Germany in 1894 professor Franz Nissl decribed the reaction of glial cells in relation to the nerve fibers in the spinal cord and highlighted their morphological changes after injury. Microglia becomes mores bigger and more abundant after injury and these glial responses can be seen as a biological reponse to promote nerve repair after injury. However, this response can go biserk and might be one of the most important mechanisms leading to neuropathic pain. 

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Toll receptor 4 and glia in neuropathic pain

Toll-like receptor 4 (TLR4) expressed on spinal microglia and astrocytes and seems to play an important role in the regulation of pain signalling in neuropathic pain. Moreover, compounds like Trental (pentoxifylline) and low dose naltrexone are interesting instruments to modulate the Toll 4 receptor and perhaps these compounds will even help in the treatment of intractable neuropathic pain.

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Small fibre neuropathic pain treated with palmitoylethanolamide (PEA)

een PEA-houdend product-thin-fibre-neuropathy.jpg Small fibre neuropathic pain is very difficult to treat. By prescribing PEA, a body own fatty compound modulating neuropathic pain via glia, we succeeded to reduce more than 50% the pain scores within 4 weeks, while the diagnostic neuropathic pain score on the DN4 decreased from 5 to 2! Small fiber peripheral neuropathy is a type of neuropathy. It is also called a small fiber neuropathy or small fiber sensory (or panful) neuropathy (SFSN) and also C fiber neuropathy. 

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CIAP and sciatic pain treated with palmitoylethanolamide (PEA)

ischialgia.jpg Severe sciatic pain and pain due to CIAP in a 80-year old lady. She could stop all analgesics after treatment with palmitoylethanolamide (PEA), and pain disappeared. Furthermore, her gait improved and the burning pain in the feet vanished too. PEA is since 2012 world wide available as the supplement PeaPure (produced in the Netherlands), and as een PEA-houdend product in Italy and Spain, produced in Italy.

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Bedsore pain treated with palmitoylethanolamide

decubitus-pea.jpg A patient suffering from neuropathic pain after a bed sore. Pain did not change under pregabaline, treatment with een PEA-houdend product decreased the pain considerably.

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Glia modulator propentofyllin not active on human non-neuronal cells

Glial cells are involved in neuropathic pain conditions. Several glial-targeted agents are in development for the treatment of pain conditions. The glial modulating agent, propentofylline, did however not decrease pain reported in association with post-herpetic neuralgia. Why? Because the human non-neuronal cells do not listen to this glia modulator, although rat non neuronal cells do….

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Visceral Pain: Global Year

2012-2013 will be the Global Year Against Visceral Pain campaign

This will be launched on Monday, October 15, 2012.

This IASP initiative will focus global attention on pain that originates in or near the internal organs of the body.
Visceral pain is the most frequent form of pain, felt by most people at one time or another, the number one reason for patients to seek medical attention, and yet it is insufficiently treated as it is considered just a symptom of an underlying disease: if we treat the disease the pain will go away – an approach that ignores that many forms of visceral pain are diseases in their own right and require focused and specific therapies.

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Cervico-thoracic or lumbar sympathectomy for neuropathic pain and complex regional pain syndrome

Complex regional pain syndrome (CRPS) is a chronic pain condition most often affecting one of the limbs (arms, legs, hands, or feet), usually after an injury or trauma to that limb. Surgical sympathectomy has long been seen as a realistic option to treat CRPS. The use of this operation that destroys some of the nerves however has always remain controversial. In a recent Cochrane analysis no evidence could be found. The conclusion was:

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Glia as target for new analgesics and palmitoylethanolamide: PEA in sciatic pain

In 2011 our institute was present at the SIAARTI, in Perugia, Italie, at the biggest Italian congres for anesthesiologists and pain specialists (SIAARTI, Società Italiana di Anestesia, Analgesia, Rianimazione e Terapia Intensiva). siaarti_2011_sciatic_pain_.png
At this congress we had the honor and pleasure to talk extensively on the efficacy of palmitoylethanolamide (PEA) and present for the first time our analysis of the efficacy and safety of this compound related to its Numbers Needed to Treat, based on a RCT with 636 patients.

We will discuss the results of this analysis based on the presentation at the SIAARTI.The entire presentation under the link, start at 1 minute 53 to skipp the Italian introduction.

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Neuropathic pain research in Germany

The doctors and researchers working in the field of neuropathic pain in Germany, are bundling insights and resources in the German Research Network on Neuropathic Pain (DFNS). The DFNS focusses on research in the field of neuropathic pain by integrating the resources of the leading centers actively involved in neuropathic pain research in Germany.

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KRN5500 and Neuropathic Pain: weak effect?

KRN5500 is a novel non-opioid analgesic agent, a semi-synthetic derivative of spicamycin: (6-[4-Deoxy-4-[(2E,4E)-tetradecadienoylglycyl]amino-L-glycero-ß-L-manno-heptopyranosyl]amino-9H-purine). Recently favorable clinical results of a Phase 2 study were reported for the primary endpoint and statistical significance was found for KRN5500 compared to placebo in a blinded, randomized, placebo controlled, dose escalation study in patients with advanced cancer and neuropathic pain.

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Alternative treatments for neuropathy and neuropathic pain

There are many different treatments for neuropathy and neuropathic pain to be found on the internet. A bewildering variety. For mainstream therapies such as painkillers for neuropathic pain, each patient will probably be able to quickly find the essence of all these treatment modalities. But for alternative treatments it is more complex.

In the articles in this section we will briefly discuss treatments for neuropathy and neuropathic pain which are not mainstream. For each treatment we will add a trafic light. A green light means this is a safe and effective treatment, based on clinical trials. A red traffic light means, this is nonsense, the therapy has been proven to be not effective, ot safe or it is just plain bullshit.  

For instance: electrical stimulation with acupuncture needles, so calles PENS has been proven to be safe and effective in the treatment of neuropathic pain. You would see a green light.

Bioresonance has been proven to be not effective and can do harm by leading patients away from  rational therapy and misleading patients. This would be clearly a red light. 

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Treatment neuropathic pain insufficient

There are many people in the Netherlands suffering from neuropathic pains, almost 1% of our entire population and nearly 150,000 new patients each year! There are a number of centers in the Netherlands where there is adequate expertise in the field of diagnosis of neuropathy. But treatment of neuropathic pain remains difficult. And this is our specialty.

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Perampanel from Eisai in neuropathic pain

perampanel.pngPerampanel from Eisai, currently in phase II for neuropathic pain. E2007 (perampanel) is a orally administered, selective non-competitive AMPA-type glutamate receptor antagonist. Other development indications: Parkinson’s disease, epilepsy, multiple sclerosis and migraine prophylaxis. In Parkinson’s disease the drug failed. Information from 2008 related to neuropathic pain states that

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Anodyne Therapy System® for neuropathy: not proven!

Surfing the net you may encounter many different treatments for neuropathy, and the anodyne therapy is one of those. In the internet you may find advertorials like the following: f you suffer from diabetic neuropathy, you may benefit from Anodyne Therapy–a non-invasive treatment that increases circulation and reduces the pain associated with peripheral neuropathy. The Anodyne Therapy System® helps to release nitric oxide from the red blood cells of patients suffering from diabetes. It does this with monochromatic infrared energy (MIRE) administered through flexible pads containing infrared diodes. 

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Treede: Redefinition and a grading system for clinical and research purposes for neuropathic pain

Treede and coworkers published a key paper in the field of the diagnosis of neuropathic pain, in Neurology 2008 (april). His article is very authorative and we will review relevant parts. They set of analysing the deficiency of the definition of neuropathic pain as given by the International Association for the Study of Pain (IASP). 

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