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

被引:18
作者
Aouad, Maya
Zell, Vivien
Juif, Pierre-Eric
Lacaud, Adrien
Goumon, Yannick
Darbon, Pascal
Lelievre, Vincent
Poisbeau, Pierrick
机构
[1] CNRS, F-67084 Strasbourg, France
[2] Univ Strasbourg, Inst Neurosci Cellulaires & Integrat, Strasbourg, France
关键词
BDNF; Central inflammation; COX2; GABA; Glycine; Microglia; Nonbenzodiazepine anxiolytic; PGE2; Spinal pain processing; FACTOR-ALPHA NEUTRALIZATION; NECROSIS-FACTOR-ALPHA; DORSAL-HORN NEURONS; RAT MODEL; NEUROPATHIC PAIN; KNEE-JOINT; PROINFLAMMATORY CYTOKINES; PERIPHERAL INFLAMMATION; EXPERIMENTAL ARTHRITIS; PROSTAGLANDIN E(2);
D O I
10.1016/j.pain.2013.11.003
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
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 3 alpha-reduced neurosteroids, the most potent positive allosteric modulator of GABAA receptor function. Here we show that a curative and a preventive treatment with 50 mg/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. (C) 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:403 / 412
页数:10
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