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Reducing this excitability could theoretically be achieved by amplifying the existing spinal inhibitory control mediated by <jats:styled-content style=\"fixed-case\">GABAA<\/jats:styled-content> receptors (<jats:styled-content style=\"fixed-case\">GABAARs<\/jats:styled-content>). In this study, we used the non\u2010benzodiazepine anxiolytic etifoxine (<jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content>) to characterize its interest as pain killer and spinal mechanisms of action. <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> potentiates <jats:styled-content style=\"fixed-case\">GABAAR<\/jats:styled-content> function but can also increase its function by stimulating the local synthesis of 3\u03b1\u2010reduced neurosteroids (<jats:styled-content style=\"fixed-case\">3\u03b1NS<\/jats:styled-content>), the most potent endogenous modulators of this receptor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The efficacy of <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> analgesia and the contribution of <jats:styled-content style=\"fixed-case\">3\u03b1NS<\/jats:styled-content> were evaluated in a rat model of mononeuropathy. Spinal contribution of <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> was characterized through changes in pain symptoms after intrathecal injections, spinal content of <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">3\u03b1NS<\/jats:styled-content>, and expression of <jats:styled-content style=\"fixed-case\">FosB<\/jats:styled-content>\u2010related genes, a marker of long\u2010term plasticity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that a 2\u2010week treatment with <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> (&gt;5\u2009mg\/kg, i.p.) fully suppressed neuropathic pain symptoms. This effect was fully mediated by <jats:styled-content style=\"fixed-case\">3\u03b1NS<\/jats:styled-content> and probably by allopregnanolone, which was found at a high concentration in the spinal cord. In good agreement, the level of <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> analgesia after intrathecal injections confirmed that the spinal cord is a privileged target as well as the limited expression of <jats:styled-content style=\"fixed-case\">FosB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">\u0394FosB<\/jats:styled-content> gene products that are highly expressed in persistent pain states.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This preclinical study shows that stimulating the production of endogenous analgesics such as <jats:styled-content style=\"fixed-case\">3\u03b1NS<\/jats:styled-content> represents an interesting strategy to reduce neuropathic pain symptoms. Since <jats:styled-content style=\"fixed-case\">EFX<\/jats:styled-content> is already prescribed as an anxiolytic in several countries, a translation to the human clinic needs to be rapidly evaluated.<\/jats:p><\/jats:sec>","DOI":"10.1002\/j.1532-2149.2013.00367.x","type":"journal-article","created":{"date-parts":[[2013,7,24]],"date-time":"2013-07-24T19:26:56Z","timestamp":1374694016000},"page":"258-268","source":"Crossref","is-referenced-by-count":42,"title":["Etifoxine stimulates allopregnanolone synthesis in the spinal cord to produce analgesia in experimental mononeuropathy"],"prefix":"10.1002","volume":"18","author":[{"given":"M.","family":"Aouad","sequence":"first","affiliation":[{"name":"Nociception and Pain Department Institut des Neurosciences Cellulaires et Int\u00e9gratives Centre National de la Recherche Scientifique and University of Strasbourg  Strasbourg 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