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Article Dans Une Revue Pain Année : 2014

Etifoxine analgesia in experimental monoarthritis: A combined action that protects spinal inhibition and limits central inflammatory processes

Résumé

Inflammatory and degenerative diseases of the joint are major causes of chronic pain. Long-lasting pain symptoms are thought to result from a central sensitization of nociceptive circuits. These processes include activation of microglia and spinal disinhibition. Using a monoarthritic rat model of pain, we tried to potentiate neural inhibition by using etifoxine (EFX), a nonbenzodiazepine anxiolytic that acts as an allosteric-positive modulator of gamma-aminobutyric acid type A (GABAA) receptor function. Interestingly, EFX also can bind to the mitochondrial translocator protein (TSPO) complex and stimulate the synthesis of 3α-reduced neurosteroids, the most potent positive allosteric modulator of GABAA receptor function. Here we show that a curative and a preventive treatment with 50mg/kg of EFX efficiently reduced neuropathic pain symptoms. In the spinal cord, EFX analgesia was accompanied by a reduction in microglial activation and in the levels of proinflammatory mediators. Using electrophysiological tools, we found that EFX treatment not only amplified spinal GABAergic inhibition, but also prevented prostaglandin E2-induced glycinergic disinhibition and restored a "normal" spinal pain processing. Because EFX is already distributed in several countries under the trade name of Stresam for its anxiolytic actions in humans, new clinical trials are now required to further extend its therapeutic indications as pain killer.
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Dates et versions

inserm-03543754 , version 1 (26-01-2022)

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Maya Aouad, Vivien Zell, Pierre-Eric Juif, Adrien Lacaud, Yannick Goumon, et al.. Etifoxine analgesia in experimental monoarthritis: A combined action that protects spinal inhibition and limits central inflammatory processes. Pain, 2014, 155 (2), pp.403-412. ⟨10.1016/j.pain.2013.11.003⟩. ⟨inserm-03543754⟩
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