Yalcin Ipek, Tessier Luc-Henri, Petit-Demoulière Nathalie, Doridot Stéphane, Hein Lutz, Freund-Mercier Marie-José, Barrot Michel
Institut des Neurosciences Cellulaires et Intégratives, Centre National de Recherche Scientifique and Université de Strasbourg, Strasbourg, France.
Neurobiol Dis. 2009 Mar;33(3):386-94. doi: 10.1016/j.nbd.2008.11.003. Epub 2008 Nov 24.
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 beta(2)-AR deficient mice, and/or that this antiallodynic action was blocked by intraperitoneal or intrathecal injection of the beta(2)-AR antagonist ICI 118,551 but not by the alpha(2)-AR antagonist yohimbine. We also showed that the anticonvulsant gabapentin was still effective in beta(2)-AR deficient mice. Our results demonstrate that beta(2)-ARs are essential for the antiallodynic action of antidepressant drugs.
神经性疼痛是一种由神经系统损伤或功能障碍引起的疾病。抗抑郁药或抗惊厥药目前是现有的最佳治疗方法。抗抑郁药缓解神经性疼痛的机制仍知之甚少。我们使用小鼠的药理学和转基因方法，评估了肾上腺素能受体（AR）在三环抗抑郁药地昔帕明、去甲肾上腺素和5-羟色胺再摄取抑制剂文拉法辛以及去甲肾上腺素再摄取抑制剂瑞波西汀作用中的影响。通过在坐骨神经周围插入套管诱导神经病变。我们发现，慢性抗抑郁药治疗可抑制野生型小鼠的套管诱导的痛觉过敏，但对β₂-AR缺陷小鼠无效，和/或这种抗痛觉过敏作用可被腹腔内或鞘内注射β₂-AR拮抗剂ICI 118,551阻断，但不能被α₂-AR拮抗剂育亨宾阻断。我们还发现抗惊厥药加巴喷丁在β₂-AR缺陷小鼠中仍然有效。我们的结果表明，β₂-ARs对抗抑郁药的抗痛觉过敏作用至关重要。
