Mechanical allodynia & Hyperlagesia - page 2 Scientific Publications

Latest publication 03/14/2020

GABAergic modulation of secondary hyperalgesia- A randomized controlled 4_way cr

The antihyperalgesic and sedative effects of the _2_subunit preferring GABAA positive allosteric modulator (GAM), N_desmethyl_clobazam (NDMC), 20...

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    [title] => GABAergic modulation of secondary hyperalgesia- A randomized controlled 4_way cr
    [paragraph] => GABAergic modulation of secondary hyperalgesia: A randomized controlled 4_way crossover trial with the alpha2_subunit preferring GABA positive allosteric modulator, N_desmethyl_clobazam in healthy volunteers 
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Authors
A Matthey, Y Daali, F Curtin, et al

 Lab
Division of Clinical Pharmacology and Toxicology, University Hospital of Geneva, Geneva, Switzerland.
Journal
European Journal of Pain
Abstract
The antihyperalgesic and sedative effects of the _2_subunit preferring GABAA positive allosteric modulator (GAM), N_desmethyl_clobazam (NDMC), 20 and 60 mg, were assessed in a randomized, placebo and active_controlled (clonazepam 1,5 mg), 4_way crossover study, in healthy volunteers, using the ultraviolet B_induced experimental pain model. Single (20, 40, 60 mg) and repeated doses (20 mg over 15 days) of NDMC pharmacokinetics were evaluated. Thirty_two subjects participated in the study. Primary outcome parameter was maximal change in the area of cutaneous UVB irradiation_induced secondary hyperalgesia (ASH). ASH decreased under all treatments. Mean (SD) relative change was 79 (22)%, 83 (24)%, 77 (30)% and 92 (16)% for placebo, NDMC20, NDMC60 and clonazepam, respectively. Neither absolute change nor relative change in ASH was significantly different between NDMC60 and placebo (mean difference = 2.3 cm2 [95% CI 4.0–8.5], p = .462 and 0.4% [_11.9 to 12.6], p = .952, respectively). An overall treatment effect was found on level of sedation. Compared to placebo, sedation was higher under clonazepam (mean difference = 39 mm [30–49] on a visual analogue scale, p < .001) while NDMC was free of sedative effect. NDMC pharmacokinetics after single doses showed poor absorption, but was linear. Steady_state plasma concentrations of NDMC20 were attained within 14 days, with low between_subjects variability. Mean steady_state concentration (CS_S, SD) reached 209 (22) ng/ml. NDMC absence of sedative effect and its overall well_characterized safety coming from years of utilization as a metabolite from clobazam, raise the prospect of dose escalating trials in patients to quantify its clinical utility.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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A quick solution to determine the mechanical sensitivity threshold in rodents (mice and rats). Now wireless, to be free from annoying cables!

This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.

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As an electronic version of the classical Von Frey Filaments esthesiometer (or aesthesiometer), the latest evolution of Bioseb's Electronic Von Frey instrument for determining the mechanical sensitivity threshold in rodents (rats and mice) is a must-have instrument for your reseach on hyperalgesia and allodynia. By measuring and recording the force at which the animal exhibits a paw withdrawal reflex, pathologies related to sensory response and hyper- or hypo-aesthesia can be studied.

The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.

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