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In this section English articles are published on neuropathy.

Patients critical about doctos’s knowledge of neuropathic pain in SCI

How do community-dwelling individuals with a traumatic spinal cord injury (SCI) see their chronic pain and how do they acquiring information. In this study the authors used a semi-structured interview and interviewed 12 individuals experiencing sipinal cord injury (SCI)-related chronic pain. This is neuropathic pain of central origine.

 

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JNJ 42160443 from Johnson in neuropathic pain

JNJ 42160443 from Johnson in neuropathic pain, phase II. Hereunder the update of clinical trials running for this compound, as of April 2010. The Janssen compound is a monoclonal antibody directed against nerve growth factor (NGF). In animal models it demonstrates potential analgesic activity. Anti-nerve growth factor monoclonal antibody JNJ-42160443 binds to NGF, and prevents its binding to the NGF receptors TrkA and p75NTR. Inhibition of this pathway may prevent neuropathic pain.

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Topical administration of ketamine and related compounds in neuropathic pain

wijze_creme_3.jpgIn our clinic we develop prototypes of transdermal creams to treat neuropathic pain. Currently we work on simple creams containing amitriptyline (5-10%) and ketamine (10%).

Here we quote from a clinical source and a patent analysis on various cream compositions for neuropathic pain, published in the VS. 

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Why do so many drugs fail in phase II?

In the internet there is a big community of specialists involved in drug R&D and at LinkedIn there are quite some interesting discussions related to topics worth while considering. The question which haunts many drug developers is: Why is it that so many drugs flunk after phase II trials? That question is also immensly important for the development of drugs in the field of chronic pain. But it is a generic question. 

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Chronic pancreatitis: neuropathy of intrapancreatic nerves

In chronic pancreatitis (CP) severe back and belly pain with caracteristics of neuropathic pain can be found. In CP there are indications of intra-organ and central neuropathic and neuroplastic alterations.

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Low dose naltrexone for MS: a pilot trial

Presentation FP48-TH-05 of the 19th World Congress of Neurology, titel: "Study of low dose naltrexone modulation of the endocannabinoid system in patients with multiple sclerosis" from the studygroup from Italy (M. Gironi ety al) discussed the use of low dose naltrexone (LDN) in Multiple Sclerosis (MS. They showed that LDN (4 mg/day) administered daily for 6 months in 40 patients with primary progressive (PP) MS (Gironi et al., 2008) was safe, well tolerated and partially efficacious on spasticity. 

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Dalfampridine: old bird poison helps MS patients walking..

In Annels of neurology an editorial on 4-Aminopyridine: New Life For an Old Drug. Fampiridine we called in in the past, it was an old bird poising at one time long ago. I have reviewed clinical data of that old potassium channel inhibitor for symptomatic improvement of MS many years ago, in order to possibly licence it in for a certain pharmaceutical company. You could function a bit better, due to an improvement of impulse conductance of the nerves. At that time, many, many years ago, I felt that the symptomatic improvement was too little and the side effects to troublesome to put development energy into the drug. Since then various pharmaceutical industries must have looked into the files of fampiridine in MS. Now, the FDA approved the drug for walking difficulties in patients suffering from MS.

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Critical illness myopathy (CIM) or critical illness polyneuropathy (CIP): bad sign!

German anesthesiologists and neurologists analysed whether there is an association between the early differentiation ofcritical illness myopathy (CIM) versus critical illness polyneuropathy (CIP) and clinical prognosis. 

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Mutiple Target Analgesia

In Patent literature sometimes great insights can be found about how to proceed in pain treatment, such as in this patent,  and we enclose here the introductrion and a part of the summary. Pain clearly is especially influenced by non-neuronal cells, is the thesis of this patent.

The current theories and treatment options for persistent pain are not satisfactory. The population of patients with chronic pain and disrupted lives grows constantly. According to the American Pain Foundation, there are 75 million Americans who have chronic pain. Pain is the second most common reason for doctor visits. Unless we can understand how pain is generated, we cannot provide a solution. Our understanding of pain has not advanced since the 1965 publication of the gate theory of pain by Canadian psychologist Ronald Meizack and British physiologist Patrick Wall. In their paper titled “Pain Mechanisms: A New Theory,” Melzack and Wall suggested a gating mechanism within the spinal cord that closed in response to normal stimulation of the fast conducting “touch” nerve fibers; but opened when the slow conducting “pain” fibers transmitted a high volume and intensity of sensory signals. The gate could be closed again if these signals were countered by renewed stimulation of the large fibers.

A recent model, known as Sota Omoigui’s Law, proposes that the origin of all pain is inflammation and the inflammatory response. This model is a dramatic and revolutionary shift from a focus on structural pathology to an understanding of the biochemical origin of Pain.

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Glia modulators for neuropathic pain

Since 1994 when Meller and colleagues for the first time demonstrated that by inhibiting astrocyte functions, neuropathic pain did not emerge, many glia modulators have been explored as new inroads in the treatment of neuropathic pain. Some specifically inhibit cytokines (like Il-18), others enhance anti-inflammatory cytokines, such as Il-10, and again others stabilize mastcell degranulation and are PARR agonists, such as palmitoylethanolamide. Here a summary:

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Pentoxyfilline as a gliamodulator

Pentoxifylline is a xantine derivate and can be given to patients with claudicatio intermittens. Because pentoxifylline inhibits cytokines (molecules that activate inflammation), this drug could be interessing for the treatment of neuropathic, and thus gliopathic pain.

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Palmitoylethanolamide and leucocyte inhibition

Palmitoylethanolamide (PEA) is a lipid amide that occurs in our bodies as well as in many mammalian tissues, and can when administered as a drug, inhibits inflammatory responses via the recent described nuclear receptor, the peroxisome proliferator-activated receptor-alpha (PPAR-alpha).

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Parkinson’s disease and modulation via endocannabinoids

Endocannabinoids are important molecules with a mutitude of actions. Endocannabinoids might play a role in Parkinon’s disease. Now that palmitoylethanolamide, a key endocannabinoid molecule, is available as a supplement, this topic seems quite important to adress. We quote from the hallmark TIPS paper The endocannabinoid system in targeting inflammatory neurodegenerative diseases.

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Ketamin might have glia as target for neuropathic pain

Glia is a new target in the treatment of neuropathic pain. Ketamine might have a mode of action related to glia hyperactivity.

The acute analgesic effects of ketamine are generally believed to be mediated by the inhibition of NMDA receptors in nociceptive neurons. The authors explored the possible effect of ketamine on spinal microglia. They found that  S-ketamine preferentially suppressed the nerve injury-induced development of tactile allodynia and hyperactivation of spinal microglia.

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Honorary Consultants Institute Neuropathic Pain

The institute of neuropathic pain closely cooperates with the Ukrainian Association for the Study of Pain, in order to exchange scientific insights and new treatment modalities in the field of neuropathic pain.

In 2010 we welcomed two colleagues from the Ukraine and since 2010

Prof. Igor Romanenko MD, PhD, neurologist, President Ukrainian Association for the Study of Pain,
and

Dr Volodymyr Romanenko MD, neurologist, Ukrainian Association for the Study of Pain, Secretary
are our honorary external consultants.

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P38 MAP kinase inhibitor, losmapimod, fails in patients with neuropathic pain after injury

The P38 MAP kinase inhibitor, losmapimod, failed to be effective in treating patients in patients with neuropathic pain after nerve injury. GlaxoSmithKline’s losmapimod was tested in  a randomized, double-blind, placebo-controlled, parallel-group trial between September 2009 and July 2010. [1]

Patients were recruited from 20 clinical centres across the European Union. The trial consisted of a screening period lasting up to 3 weeks, a 1-week baseline period, a 4-week double-blind dosing period and a follow-up period of approximately 2 weeks.

The primary efficacy measure was the mean change in average daily pain score from baseline to week 4 of treatment based on the 11-point PI-NRS 

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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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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_asterocyts_and_pyrmidal_cell.jpg

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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