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Research & Development

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

Low-grade inflammation and chronic pain

Low-grade inflammation is thought to play a role in the pathophysiology of chronic pain conditions. This is the reason why increasing numbers of pain physicians use the anti-inflammatory compound palmitoylethanolamide. Previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have only looked at a few predetermined cytokine candidates. The aim of a number of researchers […]

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Drs N. Groven and his colleagues from Norway presented a poster at the EFIC in 2017 in Copenhagen, were they explored the peripheral inflammatory character of fibromyalgia. We often recommend palmitoylethanolamide for the treatment of fibromyalgia. This is a supplement based on an endogenous molecule inhibiting inflammation (PeaPlex, Glialia). Fibromyalgia (FM) patients often experience symptoms […]

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Topical Phenytoin cream and the identification of responders and placebo responders

At the European Pain Federation (EFIC) at Copenhagen, September 2017, we could present our placebo response test at the workshop on placebo and nocebo responders. This workshop on ‘the state of the art, prediction and ethical considerations’, chaired by Dr Vase, the first presenter dr Colloca from the USA reinforced such response system to identify […]

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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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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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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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Epoxygenated fatty acids (EFAs) and neuropathic pain

Fatty acids might play a bigger role in neuropathic pain than previously thought. 

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Santhera’s Catena® in Leber’s Hereditary Optic Neuropathy

Santhera Pharmaceuticals Holding AG will present newest clinical data related to the results of a clinical trial of Catena® in Leber’s Hereditary Optic Neuropathy (LHON). Catena® is the first drug that has been evaluated in arandomized, placebo-controlled study in LHON. Catena® might protect the retinal and optic nerve cellsand thereby delay, lessen or prevent vision loss. LHON is a rare neuropathy of the eye nerves, estimated with 20,000 patients in Europe and in the United States.

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Palmitoylethanolamide: for the treatment of cannabis dependence.

Drs M. Coppola and R. Mondola from the Department of Addiction, in Alba, Italy and the Department of Mental Health, Saluzzo, Italy published an interesting paper on the putative use of palmitoylethanolamide (PEA) in the treatment of Cannabis dependency. They bring forward this hypothesis based on a variety of findings,

They point out that like cannabis, evidences suggest that PEA, as THC, has anti-inflammatory and anti-nociceptive activity in humans as well as in animal models. PEA, an anandamide congener, might have PEA has anti-craving effects in cannabis dependent patients, is efficacious in the treatment of withdrawal symptoms, produces a reduction of cannabis consumption and is effective in the prevention of cannabis induced neurotoxicity and neuro-psychiatric disorders due to its pleotropic mechanism of action.

Source: Coppola M, Mondola R. Palmitoylethanolamide: From endogenous cannabimimetic substance to innovative medicine for the treatment of cannabis dependence. Med Hypotheses. 2013 Jul 26. doi:pii: S0306-9877(13)00338-1.

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Palmitoylethanolamide (PEA), an ALIAmide regulating mast cells


Identification of palmitoylethanolamide (PEA) as regulatory mechanism for the metabolism of mast cells by Nobel Price Laureate Rita Levi Montalcini in 1993, and it’s use as a analgesic and anti-inflammatory compound

Searching for non psychoactive Cannabinoids our clinic identified in 2010 the small molecule palmitoylethanolamide (PEA) as a potent novel and promising analgesic and anti-inflammatory agent. This molecule has been developed based on the work and insights of Rita Levi Montalcini, as an off spin of her work with nerve growth factors.

As PEA, trade names PeaPure and Normast, is gaining more and more international recognition as a break through molecule in the treatment of chronic pain and inflammation, it is worth while to shortly analyze how the mast cell modulation concept, palmitoylethanolamide and the ALIA concepts came into existence.

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Reduction of PEA- FAAH in medication-overuse headache

An acute reduction of the endocannabinoid-hydrolase fatty acid amide hydrolase (FAAH) is coupled with an improvement of the facilitation of the nociceptive pathways in medication-overuse headache is the total title of a poster presentation by A. Perrotta and colleagues from a series of scientific institutions in Italy.

Medication overuse headache (MOH) is quite a problem for patients. The headaches are terrible and the idea that these hadaches increases if painkillers are ingested is couter-intuitive. Now there are clear indications Palmitoylethanolamide might be a good idea in the substitution of less painkillers and during the period of weaning off painkillers.

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Neuropathic Pain Market booming: $5.2 billion by 2018

The market for drugs to be used for the treatment of neuropathic pain is suggested to become very significantand seems to be booming: the forcast is e doubling in 10 years time up to a dassling figure of $5.2 billion by 2018! Under the titel: Research and Markets: Forecast Insight: Neuropathic Pain – Brighter Future for Pipeline Drugs with Market to Double in Value to $5.2 Billion, a press release of Datamonitor dated Monday February 15, 2010 states.

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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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GRC 15300 from Glenmark in the hands of Sanovi-Aventis

Glenmark Pharmaceuticals Ltd. (GPL) announced in 2010 that the company has entered into an agreement with Sanofi-aventis to grant Sanofi-Aventis a license for the development and commercialization of the new class of agents called vanilloid receptor (TRPV3) antagonists. This includes Glenmark’s first-in-class clinical compound, GRC 15300, currently in phase I.

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Topical low dose clonidine gel to treat Diabetic Neuropathy: phase 2 results

A phase 2b double-blind, randomized, placebo-controlled clinical trial, involving topical gel candidate ARC-4558 for the treatment of painful diabetic neuropathy produced effective results in relieving the pain, according to a press release of the company in july 2010.

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Nanorobots interacting with neurons

Nerve cells break down: spinal damage and paralysis, parkinson’s disease and nigra cells…will nanorobots ever interact with our delicate and plastic nervous system like in this simulation?

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