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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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Johnson & Johnson work on glutamate as a target for neuropathic pain

Johnson & Johnson work on glutamate as a target for neuropathic pain and in 2009 researchers from Belgium published their understanding about the role of the glutamate receptor in neuropathic hypersensitivity.

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PH-797804 in neuropathic pain: a Novel N-Phenyl Pyridinone Inhibitor of p38 MAP

A proof-of-concept study to determine if PH-797804 reduces neuropathic pain associated with post-herpetic neuralgia is under way (2010). Patients will be randomized to receive either PH-797804 or placebo for 4 weeks, during which time they will also record their pain symptoms using various pain scales. PH-797804 is a compound from Pfizer. 

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Amitriptyline cream in INP base for neuropathic pain

Despite the increasing number of registered analgesics for neuropathic pain, treating patients remains a conundrum due to poor activity of most available drugs and the occurrence of adverse drug reactions. Classical antidepressants are effective in relieving neuropathic pain, and most and the best evidence being available for amitriptyline.

Furthermore, in animal models for neuropathic pain, topical amitriptyline reduce thermal hyperalgia, mechanical allodynia, and analgesic effects can be demonstrated of perineural and transcutaneous amitriptyline administration. In our clinic we developed a superior 5% amitriptyline cream in a special developed INP base in order to treat neuropathic pain.

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Radiprodil fails in diabetic neuropathy

radiprodil.gifForest Laboratories reported that its new drug for neuropathic pain, radiprodil, had failed to achieve its objectives in stage 2 clinical trials. The medicine was developed in partnership with Hungarian drug maker Gedeon Richter, Ltd. It had been hoped that it would be useful for patients with peripheral neuropathy resulting from diabetes.

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Statin-associated myalgia and myopathy

Statin-associated myalgia and myopathy are the most important group of iatrogenic muscle disorders in current clinical practice, according to a recent overview (2010). The author states the importance of recognizing these forms of myoapthy, as: Iatrogenic muscle diseases may be caused by a wide range of therapeutic agents or recreational drugs. Their importance lies in the fact that they are potentially reversible but, if not recognized, they may result in severe disability and even death.

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Selected pharmacology of palmitoylethanolamide

The discovery of our own ‘Cannabis", the molecule anandamide, as an endogenous ligand for the cannabinoid receptors has led to a resurgence of interest in the fatty acid amides.  N-palmitoylethanolamine (PEA) is a sistermolecule of anandamide, a shorter and fully saturated analogue, and this molecule has been known since the fifties. In the sixties and seventies much research supported its use as prophylactic treatment for the flu, and the compound was on the market available as Impulsin.

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The mastcell in neuro-inflammation, pain and modulation by palmitoylethanolamide

Since 1993, after the work of the Nobel price laureate Rita Levi-Montalcini on palmitoylethanolamide and its inhibiting effects on inflammation, much happened. It seems that all Montalcini said in 1993 about inflammation, the role of the mastcell and the modulation of the mastcell by the endogenous modulator palmitoylethanolamide has been substantiated by new research.

Recently, a number of pharmacologists reviewed the literature and found new experimental data supporting the role of the mastcell in our central nervous system. They state that their experimental data strongly suggest the participation of mastcells in the processes which eventually lead to autoimmune demyelination, a kind of neuroinflammation, which is of relevance for e.g. multiple sclerosis.

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Extended release oxymorphone may help treating chronic neuropathic pain

Extended release oxymorphone may help treating chronic neuropathic pain due to a small pilot trial published during a congress.

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iNOS inhibitor KD7040 topical for neuropathic pain

In our clinicl we have good results using a topical cream based on ISDN, isosorbine dinitrate, a NOS inhibitor. The company Kalypsys is currently developing molecules targeting iNOS, a member of the nitric oxide synthase (NOS) family of enzymes.

Nitric oxide (NO) in the skin has been implicated in the pathophysiology of pain and inflammation.The lead molecule in this area of Kalypsys is is KD7040, a potent, topically administered, inhibitor of iNOS.

 

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KRN 5500 presents phase II: weak efficacy?

KRN 5500  (6-[4-Deoxy-4-[(2E,4E)-tetradecadienoylglycyl]amino-L-glycero-ß-L-manno-heptopyranosyl]amino-9H-purine) has been tested in a phase II trial and the results were presented on april 20 2010. More details will be presented in May in Athens, during the neuropathic pain congress.

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Zinc vinger binding SB-509 in diabetic neuropathy: positive phase II

On juli 1st 2010 Sangamo BioSciences announced positive Phase 2 data from its program to develop SB-509 as a treatment for diabetic neuropathy (DN). The data was gathered from Sangamo’s phase II trials that demonstrated that SB-509 treatment resulted in clinically improvements in subjects with moderate and severe DN as compared to placebo. SB-509 is an injectable plasmid encoding a DNA-binding zinc finger DNA-binding protein (ZFP) transcription factor (ZFP TF). It is designed to upregulate the endogenous expression of the gene encoding vascular endothelial growth factor (VEGF-A). VEGF-A has been demonstrated to have direct angiogenic, neurotrophic and neuroprotective properties.

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The search for the palmitoylethanolamide receptor

pea.jpegPalmitoylethanolamide is hot. It is a body-own compound which seems quite interesting for a number of clinical reasons, and most importantly for its analgesic properties in neuropathic pain. But how does it work? 

The search for the palmitoylethanolamide receptor was the title of a publication in Life Sciences, written by pharmacologists from the Department of Experimental Pharmacology, University of Naples, and the Department of Pharmacology, University of California, Irvine, USA.

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