_2-adrenoceptors are critical for antidepressant treatment of neuropathic pain-

Authors
I. Yalcin, N. Choucair-Jaafar, M. Benbouzid, L.-H. Tessier, A. Muller et al.

Lab
Centre National de la Recherche Scientifique and Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.

Journal
Annals of Neurology

Abstract
Objective: Tricyclic antidepressants (TCAs) are one of the first-line 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. Methods: 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 _2-AR was evaluated by studying _2-AR_/_ mice. We used von Frey filaments to assess mechanical allodynia. Results: The antiallodynic action of nortriptyline was not affected by cotreatment with the _2-AR antagonist yohimbine, the _1-AR antagonists atenolol or metoprolol, or the _3-AR antagonist SR 59230A. On the contrary, the _-AR antagonists propranolol or sotalol, the _1/_2-AR antagonists alprenolol or pindolol, or the specific _2-AR antagonist ICI 118,551 blocked the action of nortriptyline. The effect of nortriptyline was also totally absent in _2-AR–deficient mice. Interpretation: Stimulation of _2-AR 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 _-blockers that affect _2-AR and antidepressant drugs in patients treated for neuropathic pain.

BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)