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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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Pfizer working on new leads in neuropathic pain

Pfizer is working on consolidating its pipeline in pain, based on some new leads and other steps to strenghten their position in the market of neuropathic pain. They are working on compounds and innovations for: 

  1. Peripheral neuropathic pain
  2. Central neuropathic pain
  3. Post-operative pain
And on combination therapy for pain: Combo therapy with PF-4880682. Furthermore they are looking into new α2δ Ligands to ‘Expand a Successful Class of Drugs’

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Flupirtine from CNSBio in neuropathic pain

Flupirtine from CNSBio is in phase I for the development in neuropathic pain. However, flupirtine is an old molecule, aminopyridine. It has been used as an analgesic in the past and is still on the market in various countries.

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MDA19: pharmacological profile of cannabinoid ligand

The cannabinoid receptor 2 (CB(2)) agonists are potential therapeutic targets in the treatment of neuropathic pain. The pharmacological profile of  N’-[(3Z)-1-(1-hexyl)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide (MDA19), a CB(2) agonist suggest MDA19 could be a analgesic for the treatment of neuropathic pain.

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Cannabinoids and nerve regeneration or neurogenesis

Most people and neurologist view nerves as ‘copper ropes’ conducting electricity. If the copper rope breaks, the nerve is damaged, and the damage is for the rest of our life. This creates great nihilism for therapeutic innovations. And even more disturbing, patients feel this metaphore is a desription of reality. The message patients often get from their neurologist is: nothing can be done, what is dead remains dead….

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Fractalkine and neuropathic pain

fractalkine_1_jmkh.gifFractalkine is a remarkable chemokine constitutively expressed by neurons, and its only receptor, CX3CR1, is expressed by microglia. As we can see on the picture. Interaction leads to activated glia. The chemokine fractalkine therfore is a one of the new kids on the block in neuropathic pain and is seen as a key mediator of spinal neuronal-microglial communication. Fractalkine induces migration of inflammatory cells into inflamed tissues, thereby aggravating inflammatory tissue damage and fibrosis.

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Painkillers efficacy in 2010 less compared to 2005

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P38 MAP kinase inhibitor, losmapimod, fails in patients with neuropathic pain after injury

The P38 MAP kinase inhibitor, losmapimod, failed to be effective in treating patients in patients with neuropathic pain after nerve injury. GlaxoSmithKline’s losmapimod was tested in  a randomized, double-blind, placebo-controlled, parallel-group trial between September 2009 and July 2010. [1]

Patients were recruited from 20 clinical centres across the European Union. The trial consisted of a screening period lasting up to 3 weeks, a 1-week baseline period, a 4-week double-blind dosing period and a follow-up period of approximately 2 weeks.

The primary efficacy measure was the mean change in average daily pain score from baseline to week 4 of treatment based on the 11-point PI-NRS 

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Nerve Growth Factors as new inroads in chronic and neuropathic pain

Stakeholder Opinions: Targeting Nerve Growth Factor for Pain Therapy – Groundbreaking class to breathe new life into saturated market – this is the somewhat pompous and overdone title a new market research report from companiesandmarkets.com, published in 2010, on a new potential class of analgesics for neuropathic pain.

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JNJ 42160443 from Johnson in neuropathic pain

JNJ 42160443 from Johnson in neuropathic pain, phase II. Hereunder the update of clinical trials running for this compound, as of April 2010. The Janssen compound is a monoclonal antibody directed against nerve growth factor (NGF). In animal models it demonstrates potential analgesic activity. Anti-nerve growth factor monoclonal antibody JNJ-42160443 binds to NGF, and prevents its binding to the NGF receptors TrkA and p75NTR. Inhibition of this pathway may prevent neuropathic pain.

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CNSB015 at Third International Congress on Neuropathic Pain in Athens, Greece

Relevare Pharmaceuticals Ltd. presented results for CNSB015 (flupirtine), at the Third International Congress on Neuropathic Pain on May 27 -30 in Athens, Greece, which we visited. Flupirtine belongs to the class of aminopyridines, like fampyridine used in MS, and is a centrally acting nonopioid analgesic. It is on the market in Europe since 1984 under the names Katadolon and Trancolong. It is a non-opioid, non-NSAID, non-steroidal analgesic. Flupirtine therefore is an already established clinical analgesic for musculoskeletal pain. 

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AstraZeneca and neuropathic pain

AstraZeneca, a pharmaceutical company, has three compounds in clinical development for neuropathic pain:

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Il-17: new target in neuropathic pain

Il-17 is a pro-inflammatory cytokine and this molecule plays a certain role in neuropathic pain.

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