Instituut voor Neuropathische Pijn

Home > English articles > Research & Development

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 […]

Lees meer...

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 […]

Lees meer...

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 […]

Lees meer...

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 […]

Lees meer...

Chronic Pain Trials considerations

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

Lees meer...

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 […]

Lees meer...

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.

Lees meer...

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 […]

Lees meer...

Global Burden of Neuropathic Pain

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

Lees meer...

Sodium channel function in neuropathic pain

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

Lees meer...

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 […]

Lees meer...

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.

Lees meer...

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.

Lees meer...

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 […]

Lees meer...

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 […]

Lees meer...

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, […]

Lees meer...

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 […]

Lees meer...

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 […]

Lees meer...

ARC-4558, transdermal clonidine gel for neuropathic pain

ARC-4558 is the code for a transdermal gel in  development for the treatment of neuropathic pain. The gel is being developed by Arcion Therapeutics, Inc. and the company received in february 2010 $8 million to further develop this innovative gel. Arcion is a socalled venture backed clinical biotechnology company, focussing on pain treatment.  

Lees meer...

Idebenone under orphan drug development for Leber’s hereditary optic neuropathy

Idebenone is a variant of Q10 and is under development for orphan indications such as hereditary ataxia as well as for Leber’s hereditary optic neuropathy. On 15 February 2007, orphan designation (EU/3/07/434) was granted by the European Commission to Santhera Pharmaceuticals (Deutschland) GmbH, Germany, for idebenone for the treatment of Leber’s hereditary optic neuropathy.

Lees meer...

GRC 15300, a Vanilloid (TRPV)3 antagonist for neuropathic pain

Glenmark Pharmaceuticals Ltd. (GPL) announced in 2009 that its candidate for Neuropathic pain, GRC 15300 has been filed for Phase I trials. GRC 15300 is descibed as a Transient Receptor Potential Vanilloid (TRPV)3 Antagonist.

Lees meer...

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.  

Lees meer...

PEA: Evolution in pharmacological thinking: palmitoylethanolamide

palmitoylethanolamide.jpg The rising of concepts in pharmacology is a highly interesting topic. The discovery of the Cannabis receptors and the nuclear PPAR receptors have been the base of a total new understanding of may important homeostatic physiological medhanisms in our body. [1] These discoveries were necessary for us to understand the analgesic and anti-inflammatory activity of the body-own fatty amide palmitoylethanolamide. This molecule was identified as an important modulator during tissue stress as in chronic inflammation and pain and during tissue disttruction such as in ischemia. Palmitoylethanolamide (PEA) is a foordcomponent known already for more than 50 years. PEA is also a molecule widely present in animals and mammals, only it cannot be found in insects. Palmitoylethanolamide is synthetized and metabolized in animal cells via a number of enzymes and it excerts a multitude of physiological functions, related to metabolic homestasis. PEA and has been identified already in the 50s of last century as a therapeutical principle with potent anti-inflammatory properties.  Since 1975 its analgesic properties were noticed and explored in a variety of painstates. Since 2008 palmitoylethanolamide (PEA) is available as dietfood for medical purposes in countries in Europe (Italy, Spain, Germany) under the brandname Normast, produced by the Italian company Epitech. Currently palmitoylethanolamide is evaluated as special diet-treatment for Inflammatory Bowel Syndrome under te brandname Recoclix by CM&D Pharma Ltd and Nestlé. Since 2012 palmitoylethanolamide is also available under the brandname PeaPure, produced by the company Russell Science Ltd. More info in PEA under this link The history of palmitoylethanolamidel started in 1954 with a publication addressing the anti-inflammatory properties of egg yolk (see figure 1). Findings that egg yolk appeared to be some sort of ‘medical diet-food avant la lettre’ and the fact that extracts from egg yolk and peanut oil possessed anti-inflammatory activities, were discussed in that paper. Research on PEA has been conducted for more than 50 years and over 300 papers are referenced in Pubmed, describing the physiological properties of this endogenous modulator and its pharmacological and therapeutical profile. The history of the emergence of insights in the biological roles this molecule might play after its identification in 1957 is worth telling. It demonstrates the close interrelation between the scientific contex and the development of scientific facts. It also shows that plausible explanations of the mechanism of action of drugs are required before a treatment concept will be explored in more detail in science and in the clinic. Without a satisfactory explanary concept, efficacy of a compound alone will not be enough to convince the scientific community. The case of PEA demonstrates this scientific sociological finding, and PEA research sunk in oblivion in the period were no mechanism of action was convincingly demonstrated.

Lees meer...

Adenosine agonists and neuropathic pain

Adenosine is a neuromodulator that interacs with four adenosine receptors, A(1), A(2A), A(2B) and A(3). Adenosine receptors are new inroads in treating neuropathic pain. Even better, these compounds are inroads to treating gliopathic pain. Gliopathic pain is a new name for the chronic wind-up state of glia and neurons in chronic painstates we see in diabetic neuropathy, herpes zoster and many related painstates.

Lees meer...

Neuronal damage leads to increase production palmitoylethanolamide and other endocannabinoids

Neuronal damage as assessed by transection of long-range projections apparently provides a strong time-dependent and area-confined signal for de novo synthesis of various endocannabinoids, presumably to restrict neuronal damage. In an elegant study Sonja Kallendrusch and colleagues pointed out some recent studies demonstrating the neuroprotective properties of endocannabinoids in various models of neuronal lesion in vitro and in vivo. Palmitoylethanolamide, they emphesised, mediates its neuroprotective effects via dual PPAR alpha activation on microglial cells and neurons.

Lees meer...

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.

Lees meer...

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. 

Lees meer...

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.

Lees meer...

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.

Lees meer...

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.

Lees meer...