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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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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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Zinkvinger ligand SB-509 for diabetic neuropathy

The pharmaceutical company Sangamo BioSciences Inc. announced in January 2009 to start a new phase IIb study to analyse the efficacy and safety of their new compound, SB-509, a ligand for the so-called zinc finger proteins, for moderate to severe diabetic neuropathy.

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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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Measuring outcome in neuropathic pain trials

neupsig1.jpgDr. Nadine Attal from INSERM, discussed measurements in RCT’s of neuropathic pain and showed that there are great number of pain scales and questionnaires that have been used in clinical trials to assess the efficacy of interventions in neuropathic pain, varying from a simple visual analogue scale (VAS) or the numerical rating scale (NRS) to assess pain intensity to more complex multidimensional scales to assess pain, sleep, depression, quality or life or disability.NRS and VAS remain both the most suitable instruments to assess effects of treatment on pain intensity. Furthermore, clinical global impression of doctors (CGI) and responder rates are recommended for the assessment of overall change of neuropathic pain due to treatment.

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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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Antidepressants into low back pain: duloxetine (Cymbalta®)

Given the fact that most antidepressants are not active in mild to moderate depression, it is a bit odd that the Food and Drug Administration has approved in 2010 the anti-depressant Cymbalta® for a different use, which is just as vague as mild and moderate depression: low back pain and osteoarthritis.  

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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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Bupivacaine Patch, Eladur, in Post- Herpetic Neuralgia

Bupivacaine is a locally acting anesthetic agent, therefore systemic plasma concentrations is not relevant. The company Durect is  developing a transdermal bupivacaine patch (ELADUR) based on their proprietary TRANSDUR transdermal technology intended to provide continuous delivery of bupivacaine for up to three days from a single patch. ELADUR might have several potential advantages compared with currently marketed lidocaine patches, including extended duration of action and better wearability.

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NGX-1998, a non-patch liquid formulation of capsaicin

NeurogesX, Inc. developed Qutenza, a dermal patch containing capsaicin, and proceeeds working in this field. They focus now on various other pain killers, and in the pipeline we find NGX-1998, a non-patch liquid formulation of capsaicin for neuropathic pain, NGX-1576, NGX-9674, and NGX-5752 prodrugs of acetaminophen for acute pain, NGX-6052, an opioid prodrug for chronic pain.

 

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AGN-209323 from Bristol-Myers Squibb in neuropathic pain

Bristol-Myers Squibb Company (NYSE: BMY) and Allergan, Inc. (NYSE: AGN) announced in March 2010 a global agreement for the development and commercialization of AGN-209323, a Phase II, orally administered small molecule for neuropathic pain, through a potential novel undisclosed mechanism of action. AGN-209323 was discovered as part of collaboration between Allergan and ExonHit Therapeutics SA.

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Nerve cell regeneration and the receptor called DCC (Deleted in Colorectal Carcinoma)

Researchers from the university of Montreal published in Cell an article that gives some new insight in the issue of nerve cell regeneration. "We found an alternate way that helps nerve cells respond quickly and locally," sayd one of the authors of the paper, Philippe P. Roux, a professor of pathology and cell biology and a researcher at the University of Montreal Institute for Research in Immunology and Cancer (IRIC). He sees new therapeutic targets in future based on this principle:  "We can envisage manipulating this alternate mechanism to make cells respond locally to their environment. Our findings mean that scientists must consider a new way that cells organize themselves to perform essential functions."

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Critical illness myopathy (CIM) or critical illness polyneuropathy (CIP): bad sign!

German anesthesiologists and neurologists analysed whether there is an association between the early differentiation ofcritical illness myopathy (CIM) versus critical illness polyneuropathy (CIP) and clinical prognosis. 

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