{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:07:09Z","timestamp":1792735629157,"version":"4.5.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,3,3]],"date-time":"2009-03-03T00:00:00Z","timestamp":1236038400000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2009,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Tricyclic antidepressants (TCAs) are one of the first\u2010line pharmacological treatments against neuropathic pain. TCAs increase the extracellular concentrations of noradrenaline and serotonin by blocking the reuptake transporters of these amines. However, the precise downstream mechanism leading to the therapeutic action remains identified. In this work, we evaluated the role of adrenergic receptors (ARs) in the action of TCAs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used pharmacological and genetic approaches in mice to study the role of ARs in the antiallodynic action of the TCA nortriptyline. Peripheral neuropathy was induced by the insertion of a polyethylene cuff around the main branch of the sciatic nerve. The specific role of \u03b2<jats:sub>2<\/jats:sub>\u2010AR was evaluated by studying \u03b2<jats:sub>2<\/jats:sub>\u2010AR<jats:sup>\u2212\/\u2212<\/jats:sup> mice. We used von Frey filaments to assess mechanical allodynia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The antiallodynic action of nortriptyline was not affected by cotreatment with the \u03b1<jats:sub>2<\/jats:sub>\u2010AR antagonist yohimbine, the \u03b2<jats:sub>1<\/jats:sub>\u2010AR antagonists atenolol or metoprolol, or the \u03b2<jats:sub>3<\/jats:sub>\u2010AR antagonist SR 59230A. On the contrary, the \u03b2\u2010AR antagonists propranolol or sotalol, the \u03b2<jats:sub>1<\/jats:sub>\/\u03b2<jats:sub>2<\/jats:sub>\u2010AR antagonists alprenolol or pindolol, or the specific \u03b2<jats:sub>2<\/jats:sub>\u2010AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in \u03b2<jats:sub>2<\/jats:sub>\u2010AR\u2013deficient mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Stimulation of \u03b2<jats:sub>2<\/jats:sub>\u2010AR is necessary for nortriptyline to exert its antiallodynic action against neuropathic pain. These findings provide new insight into the mechanism by which antidepressants alleviate neuropathic pain. Our results also raise the question of a potential incompatibility between \u03b2\u2010blockers that affect \u03b2<jats:sub>2<\/jats:sub>\u2010AR and antidepressant drugs in patients treated for neuropathic pain. 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