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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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New insights at world congress on pain, 2012: acute and presistant pains

Michael W. Salter, MD, PhD, Neurosciences & Mental Health Program, Hospital for Sick Children presented: AN UPDATE ON THE NEUROBIOLOGY OF ACUTE AND PERSISTENT PAIN

Major advances have been made recently in understanding the pathobiology of acute and persistent pain at the molecular, cellular and neural systems levels. Thus, chronic pain may be conceptualized not as a symptom of disease but rather a disease unto itself.

The speaker elucidated on peripheral and spinal cord mechanisms of pain neuroplasticity through illuminating neuron-neuron synaptic plasticity and the emergent role of neuron-glia signaling, particularly in neuropathic pain.

He discussed the roles of plasticity and signaling in brain nociceptive networks in pain hypersensitivity. Furthermore he described the critical role of descending inhibitory and facilitatory modulation in gating persistent pain.

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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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Mast cells , periapical inflammation, peridontitis and palmitoylethanolamide

Among the cells involved in immune and inflammatory responses in periodontal disease, mast cells seem to play a major role. This is important as mast cell hyperactivity can be inhibited by the natural compound palmitoylethanolamide.

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Adelmidrol: a new ALIAmide for chronic inflammation


ADELMIDROL: a new topical ALIAmide for chronic inflammation

Adelmidrol is
the diethanolamide derivative of azelaic acid, i.e., naturally occurring
dicarboxylic acid that has long proven to be an effective topical treatment for
human inflammatory skin disorders (1), and whose mechanism of action have been
recently and thoroughly investigated (2).

Similarly to the anti-inflammatory
and anti-nociceptive compound palmitoylethanolamide (PEA) (3-17), adelmidrol
belongs to the aliamide family, a group of fatty acid derivatives with
cannabimimetic properties, able to control the event of mast cell (MC)
hyper-reactivity in several pathophysiological and pathological conditions (5).

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Capnellene from coral as a new lead for treating neuropathic pain

A Coral in the sea around Taiwan might produce a new lead for the treatment of neuropathic pain.

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Clinical trial methodology in neuropathic pain

The EMEA published a guideline on how to conduct studies in neuropathic pain, in 2007. It is worth while quoting from this guideline:

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Topical administration of ketamine and related compounds in neuropathic pain

wijze_creme_3.jpgIn our clinic we develop prototypes of transdermal creams to treat neuropathic pain. Currently we work on simple creams containing amitriptyline (5-10%) and ketamine (10%).

Here we quote from a clinical source and a patent analysis on various cream compositions for neuropathic pain, published in the VS. 

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Botuline not for Allodynia in Complex Regional Pain Syndrome

Neurologists from the Department of Medicine, University of Florida, Gainesville, Florida and the West Haven Veterans Administration Hospital, West Haven, Connecticut, USA investigated the efficacy and tolerability of Botulinum toxin A in allodynia of patients with complex regional pain syndrome. 

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