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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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PERIPHERAL INFLAMMATION IN FIBROMYALGIA

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 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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Metabolism and degradation of palmitoylethanolamide

Metabolism and degradation of palmitoylethanolamide, a short analysis of a special therapeutic enodcannabinoid.

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Palmitoylethanolamide: a natural protector against lipid peroxidation

N-Acylethanolamines (NAEs) (fatty acid ethanolamides) are naturally occurring hydrophobic molecules usually present in a very small amount in many mammalian tissues and cells [1] and [2]. Moreover, NAEs are normally present in biological fluids, such as blood [2], in very low concentrations. The physiological levels of important NAEs in mammalian blood plasma are in the range 2.8–5.2 pmol/ml for anandamide (AEA); 9.4–16.7 pmol/ml for PEA; 8.1–10.3 pmol/ml for oleylethanolamide (OEA) [2], [3] and [4]. However, the NAEs levels in blood plasma could be modified in pathological conditions, e.g., the physiological concentrations of AEA in human plasma are 4 pmol/ml, but these concentrations are increased up to 18–30 pmol/ml in sera of patients with endotoxic shocks [5]. In vivo studies demonstrated that NAEs could accumulate in injured tissues, such as, e.g., in myocardium infarcted areas [6], and in post decapitative brain ischemia [7].

And 

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TRO19622, Olesoxime in painful neuropathy

TRO19622 is the code name for the substance olesoxime currently being studied for painful neuropathy. It is a cholesterol-like substance that is designed to be a treatment of a serious disease, such as amyotrophic lateral sclerosis. Animal studies showed the neuroprotective activity, based on the its mechanism of action within the nerve cell.Trophos SA,is developing therapeutics from discovery to clinical validation for indications with under-served needs in neurology and cardiology.Olesoxime is tested in an ongoing pivotal efficacy study in amyotrophic lateral sclerosis, snd efficacy results are expected in 2011.

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ADL-5859 in neuropathic pain

ADL-5859 is a delta agonist for the opiod receptor family, and it might be of use for the treatment of neuropathic pain, by inducing less side effects as the current opioids. The compound is developed by Adolor Corporation (this is alsoi the Originator) and the compound is in phase II.

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Melatonin: protective in chemotherapy for neuropathy?

Melatonin demonstrated neuroprotective effects in a variety of animal studies and has been suggested to decrease adverse reactions of chemotherapy including neuropathy. In a pilot trial melatonin, 21 mg before sleep, given during taxane chemotherapy for breast cancer, decreased the incidence and severity of neuropathy.

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Dexpramipexole, and dose-dependent slowing of decline in ALS

Dexpramipexole is an enantiomer, of the dopamine agonist pramipexole, used in Parkinson disease. It is the right-handed isomere and it is practically devoid from all the dopaminergic effect. Preclinical work indicates dexpramipexole might have neuroprotective properties, probably due to its ability to prevent mitochondria from developing leaky membranes when under stress. Therefore it has been taken into development in an orphan indication, amyotrophic lateral sclerosis, ALS, or Lou Gehring disease as the Americans call it. (Should actually been called Charcot’s disease, as he first described ALS more than 100 years ago).

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Migraine and mast cells

mast_cell_jmkh.gifThe pathophysiology of migraine is complicated. Since some years a new dimension has opened, based on our insight in the behaviour of the mast cell in meningen. Migraine occur in nearly 1 in 5 adults in the US, are migraine attacks precipitated by stress, and are also associated with high disability, medical and economical costs and loss of quality of life. There are more than 74 million migraine patients in the US, France, Germany, Italy, Spain, and the UK in 2002 and the migraine drug market estimated at $2.86 billion in 2002 expecting to double by 2012….

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