Characterization of the fast GABAergic inhibitory action of etifoxine during spinal nociceptive processing in male rats. (April 2015)

• Record Type: Journal Article
• Authors: Juif, P.E.; Melchior, M.; Poisbeau, P.
• Is Part Of: Neuropharmacology. Volume 91(2015)
• Page Start: 117
• Page End: 122
• Publication Date: 2015-04
• Subjects: Nociception -- Pain -- Spinal cord -- In vivo electrophysiology -- GABAA receptors -- Synaptic plasticity; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2014.12.022
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Etifoxine (EFX) is a non-benzodiazepine anxiolytic which potentiate GABAA receptor (GABAA R) function directly or indirectly via the production of 3α-reduced neurosteroids. The later effect is now recognized to account for the long-term reduction of pain symptoms in various neuropathic and inflammatory pain models. In the present study, we characterized the acute antinociceptive properties of EFX during spinal pain processing in naive and monoarthritic rats using in vivo electrophysiology. The topical application of EFX on lumbar spinal cord segment, at concentrations higher than 30 μM, reduced the excitability of wide dynamic range neurons receiving non-nociceptive and nociceptive inputs. Windup discharge resulting from the repetitive stimulation of the peripheral receptive field, and recognized as a short-term plastic process seen in central nociceptive sensitization, was significantly inhibited by EFX at these concentrations. In good agreement, mechanical nociceptive thresholds were also significantly increased following an acute intrathecal injection of EFX. The acute modulatory properties of EFX on spinal pain processing were never seen in the simultaneous presence of bicuculline. This result further confirmed EFX antinociception to result from the potentiation of spinal GABAA receptor function. Highlights: Etifoxine inhibits spinal processing of noxious and non-noxious informations. Etifoxine increase the activation threshold of A-beta, A-delta and C primary afferents. This Inhibitory action is mediated by GABAA receptors. Windup is limited by etifoxine in naïve rats but not in monoarthritic pain condition.