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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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NMDA receptor: target for new developments in neuropathic pain

The NMDA receptor (NMDAR) received a new wave of attention as a target receptor for the development of new drugs for the treatment of neuropathic pain. A substantial body of data supports the expectation that a safe, potent, N-methyl-D-aspartate receptor (NMDAR) blockers would offer symptomatic relief from neuropathic pain. NMDAR stimulation is linked to sensitization of dorsal horn neurons and thus has a direct link to pain and hyperalgesia. Here some of these new R&D activities related to NMDAR ligands. 

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Ketamine in neuropathic pain

ketamine.jpegKetamine is an old drug, and has been in clinical practice for nearly 40 years, but we should not forget this drug for the treatment of neuropathic pain, and we should not be too conservative exploring ketamine as a treatment for otherwise treatment refractory neuropathic pain patients. Ketamine can be used in various ways, as infusions, oral, rectal, intranasal and transdermal. 

As an analgesic drug, doses used are much lower compared to dose-ranges used in anesthesiological practices. Furthermore, the whole story of S-ketamine being less psychoiactive compared to R-ketamine is based on old literature, with very small groups of patients, non-relaible biological read outs, such as the EEG and animal studies with very little relevance for the human species.  

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Avigen AV411 as a glia modulator in neuropathic pain

AV411 is orally bioavailable small molecule, which is characterized as a glial attenuator, that suppresses pro-inflammatory cytokines IL-1 beta, TNF alpha, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10. It is under devellopment by Avigen, Inc. (Nasdaq:AVGN), a biopharmaceutical company developing innovative therapies for the treatment of neurological conditions.

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Astra-Zeneca compound AZD2423 fails in neuropathic pain: posttraumatic neuralgia.

The Astra-Zeneca compound AZD2423, a novel chemokine receptor 2 (CCR2) antagonist, fails in treating neuropathic pain in posttraumatic neuralgia. This is the result of a phase II trial dose-finding in 133 patients with posttraumatic neuralgia. Patients were equally randomized to 28days’ oral administration of 20mg AZD2423, 150mg AZD2423 or placebo.

 

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Patients critical about doctos’s knowledge of neuropathic pain in SCI

How do community-dwelling individuals with a traumatic spinal cord injury (SCI) see their chronic pain and how do they acquiring information. In this study the authors used a semi-structured interview and interviewed 12 individuals experiencing sipinal cord injury (SCI)-related chronic pain. This is neuropathic pain of central origine.

 

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Santhera’s Catena® in Leber’s Hereditary Optic Neuropathy

Santhera Pharmaceuticals Holding AG will present newest clinical data related to the results of a clinical trial of Catena® in Leber’s Hereditary Optic Neuropathy (LHON). Catena® is the first drug that has been evaluated in arandomized, placebo-controlled study in LHON. Catena® might protect the retinal and optic nerve cellsand thereby delay, lessen or prevent vision loss. LHON is a rare neuropathy of the eye nerves, estimated with 20,000 patients in Europe and in the United States.

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Palmitoylethanolamide (PEA), an ALIAmide regulating mast cells

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Identification of palmitoylethanolamide (PEA) as regulatory mechanism for the metabolism of mast cells by Nobel Price Laureate Rita Levi Montalcini in 1993, and it’s use as a analgesic and anti-inflammatory compound

Searching for non psychoactive Cannabinoids our clinic identified in 2010 the small molecule palmitoylethanolamide (PEA) as a potent novel and promising analgesic and anti-inflammatory agent. This molecule has been developed based on the work and insights of Rita Levi Montalcini, as an off spin of her work with nerve growth factors.

As PEA, trade names PeaPure and Normast, is gaining more and more international recognition as a break through molecule in the treatment of chronic pain and inflammation, it is worth while to shortly analyze how the mast cell modulation concept, palmitoylethanolamide and the ALIA concepts came into existence.

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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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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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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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Low Doses of Palmitoylethanolamide: a selective GPR55 agonist

GPR55 receptor is highly expressed in large dorsal root ganglion neurons of spinal cord.

Several mechanisms have been suggested for the antinociceptive and anti-inflammatory actions of PEA. The relative contribution of cannabinoid CB1, vanilloid and PPARγ to PEA-induced antinociception effects has been shown in previous studies. 

The antinociceptive effect of PEA as a selective GPR55 agonist/weak cannabinoid receptor agonist was studied in a rat model. Based on the results the authors suggested that GPR55 receptors are involved in pain modulation and could be considered as an important target for antinociceptive therapies. 

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Horizant, gabapentin enacarbil, not yet on the market

In  February 2010 gabapentin enacarbil for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) was not receiving approval by the FDA due to concerns regarding findings of pancreatic acinar cell tumors in rats.

Horizant, is a prodrug of Pfizer’s gabapentin. 

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