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Research & Development

Drug Development Issues Related To New Compounds For Treating Neuropathic Pain And Neuropathy Are Presented Here.

Topical TV-45070 8% ointment in herpes zoster pain not effective

Teva Pharmaceutical Industries Ltd. at the end of June 2017 disclosed the results of a Phase II study analysing topical TV-45070 4% and 8% oil in patients with post-herpetic neuralgia (PHN). The ointment treatment (twice a day) did not reduce the primary endpoint, pain measured via the NRS, at week four compared to placebo. However, there were […]

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Chronic Pain Trials considerations

Chronic Pain Trials are not easy to conduct: some relevant issues are discussed.

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Neuropathic Itch, its neurophysiology and putative treatment

At the plenary session at the NeuPSIG 2017 at Gothenburg, Sweden a topic discussed was Neuropathic Itch. A state of the art lecture was given by  Sarah Ross, USA In PubMed only few entries can be found on neuropathic itch, and no clear therapies are known. Many neuropathic pain conditions have an itch component, such as post […]

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Neuropathic Pain Treatment Update at NeuPSIG 2017

Neuropathic Pain Treatment Update : an overview of recent neuropathic pain treatments show especially sodium channel blockers are hot in the early clinic.

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Topical treatment in Chronic Pelvic Pain

Chronic Pelvic Pain: difficult to treat! At the poster sessions atthe NeuPSIG 2017 at Gothenburg, Sweden a poster was presented from the Albany Medical Centre, claiming that in chronic pelvic pain local small fibre neuropathic changes could be detected. This was concluded based on biopsies of the skin. SFPN was suggested to be screened as […]

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Global Burden of Neuropathic Pain

Global Burden of Disease discussed in the light of neuropathic pain.

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Sodium channel function in neuropathic pain

Sodium channels were discussed as new inroads for reducing neuropathic pain.

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Repositioning of Amantadine and phenytoin: patent protected strategies

Repositioning (or repurposing) of old not-patent protected drugs in new, off label indications leads to quick development times and cheaper developments. However, one needs to overcome a number of hurdles to reach a successful repurposing of such old drugs. Athors are quite experienced in repositioning phenytoin anno 2017 as a topical analgesic. In the enclosed […]

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CR845 (Difelikefalin), A Kappa Receptors Agonist In Phase III By CARA Therapeutics

CR845: (difelikefalin), a peripheral opioid agonist currently developed by Cara Therapeutics, an analysis.

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Phenytoin cream normalizes neural overactivity in skin in neurogenic inflammation

Phenytoin cream is a newly developed cream by the Institute of Neuropathic Pain and protected by 2 patents, filed on December 6th, 2016. The cream contains 5 or 10% phenytoin and here we picture one of the mechanisms of action, via the keratinocyte.

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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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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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Taurine for painful diabetic neuropathy

taurine.jpegTaurine 3,000 mg/day (3 capsules) orally vs placebo 3 capsules daily for 12 weeks is evaluated currently in a RCT in the UK. The idea of the trial is that taurine depletion contributes to the development of painful Diabetic Neuropathy (DN). This rationale is based on:  

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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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Axonal regeneration: the ‘signaling endosome’ model

Distal axonal degeneration is a hallmark of many neuropathies. Traditionally we tended to think in a simpel degeneration-regeneration model. The celbody of each neuron, based on the functions of its residing nucleus, is key in regeneration, and all regeneration processes are anterograde. Failure of metabolic support for the cellbody causes an impairement in the function of the axon, due to the fact that the axon itself is poorly inhabited by ribosomes and mitochondia and thus the axon is totally dependent on support from its master, the cellbody. In 1997 Spencer at all described the degeneration proces using an analogy of the farthest meaddow, which is the first to be drowned from water support, if the waterpump fails. These analogies and metaphors always play a big role in our understanding and our apporach of scientific problems and clinical problems.     

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PEA, Palmitoylethanolamide per os active in different animal models

Palmitoylethanolamide (PEA) has been evaulated in many different animal models. Per os model is important to highlight, as it comes close to dosing in man. In different models PEA has been dosed orally. In a ratmodel four different doses of palmitoylethanolamide were given per os; 1, 3, 5, 10 mg kg(-1); p.o. and compared to the inhibitor of COX, indomethacine. In two depression related models in mice PEA was compared to fluoxetine. In all models PEA was biological active.

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AL-309: Efficacy in animal models of neuropathy and neuropathic pain

AL-309: Efficacy in animal models of neuropathy and neuropathic pain. According to a press release of the company, and we quote:

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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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Ibudilast, XT101 in neuropathic pain

The glial blocker XT101 demonstrated in the preclinical phase to be able to upregulates IL-10. It is developed by Xalud Therapeutics, Inc. Data on AV411 (ibudilast) has been presented by Paul Rolan, M.D., FRACP, Professor of Pharmacology, University of Adelaide, Australia, at the 10th International Conference on the Mechanisms and Treatment of Neuropathic Pain held in Salt Lake City, Utah, in 2007.

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Focus on Palmitoylethanolamide in IASP journal PAIN

In the recent journal PAIN of the IASP ( number 3 march 2013) an editorial as well as a research paper is devoted to natural moleucles such as palmitoylethanolamide. In the editorial comment, by BK Taylor (N-acylethanolamine acid amidase (NAAA), a new path to unleash PPAR-mediated analgesia) he writes:

Antihyperalgesic effects are produced by endogenously-generated PPAR activators. Of particular importance to pain research are the fatty acid ethanolamides, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), both of which bind with high affinity to PPARα.

In neurons, glia, and inflammatory cells, PEA and OEA are not stored, but rather are made on demand – endogenous levels are regulated by the relative activity of biosynthetic and degradative enzymes. Animal studies convincingly demonstrate that PEA exerts a broad spectrum pain inhibition that can be reversed with PPARα antagonists and this inhibition does not occur in deletion mutant mice lacking PPARα. 

Palmitoylethanolamide is approved in some countries  as a dietary supplement in humans, and preliminary but intriguing clinical trials and case studies suggest that oral PEA is effective for a variety of pain syndromes …

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Clinical trial methodology in neuropathic pain

The EMEA published a guideline on how to conduct studies in neuropathic pain, in 2007. It is worth while quoting from this guideline:

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Botuline not for Allodynia in Complex Regional Pain Syndrome

Neurologists from the Department of Medicine, University of Florida, Gainesville, Florida and the West Haven Veterans Administration Hospital, West Haven, Connecticut, USA investigated the efficacy and tolerability of Botulinum toxin A in allodynia of patients with complex regional pain syndrome. 

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Mast cells and abdominal aneurysms

Mast cells are moving into the central field of attention for a variety of disorders. Mast cells have previously been seen as a kind of Cinderella cell, as professor Rita Levi Montalcini pointed out, shortly after her Nobelprice for growth factors, but are in fact ‘prima dona’ cells. These cells might also participate  in the pathogenesis of abdominal aortic aneurysm (AAA).

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AM1241, a Canabinoid ligand against cancer pain

Cannabis is an age-old analgesic which we use off and on for the treatment of severe neuropathic pain, as an adjunct to other treatment modalities. Now, a new study demonstrates the putative positive effect of  a new Cannabinoid CB(2) agonists , AM1241.

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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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Bias in preclinical pharmacology: the abstract deceives!

Preclinical researchers do not fully understand clinical studies and clinicans fail to grasp preclinical work. One of the reasons is the mistake many of us make in reading scientific papers. We start screening the abstract in Pubmed and jump to conclusions, sometimes or most of the time without reading the full paper. This happens frequently and will be demonstrated by an recent example, the publication of a key paper on pain treatment using opioids together with an opioid antagonist in the peer reviewed journal Molecular Pain.

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Analgesic creams from the institute of neuropathic pain

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Topical treatment of neuropathic pain

Topical analgesic creams to treat pain and tingling may have many advantages over systemic treatment with analgesics: 

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