β2-adrenoceptors are essential for desipramine, venlafaxine or reboxetine action in neuropathic pain

Neuropathic pain is a disease caused by a lesion or dysfunction of the nervous system. Antidepressants or anticonvulsants are presently the best available treatments. The mechanism by which antidepressants relieve neuropathic pain remains poorly understood. Using pharmacological and transgenic approaches in mice, we evaluated adrenergic receptor (AR) implication in the action of the tricyclic antidepressant desipramine, the noradrenaline and serotonin reuptake inhibitor venlafaxine, and the noradrenaline reuptake inhibitor reboxetine. Neuropathy was induced by cuff insertion around the sciatic nerve. We showed that chronic antidepressant treatment suppressed cuff-induced allodynia in wild-type mice but not in β2-AR deficient mice, and/or that this antiallodynic action was blocked by intraperitoneal or intrathecal injection of the β2-AR antagonist ICI 118,551 but not by the α2-AR antagonist yohimbine. We also showed that the anticonvulsant gabapentin was still effective in β2-AR deficient mice. Our results demonstrate that β2-ARs are essential for the antiallodynic action of antidepressant drugs.