Delta-opioid receptors are critical for tricyclic antidepressant treatment of neuropathic allodynia

被引:81
作者
Benbouzid, Malika [1 ]
Gaveriaux-Ruff, Claire [2 ]
Yalcin, Ipek [1 ]
Waltisperger, Elisabeth [1 ]
Tessier, Luc-Henri [1 ]
Muller, Andre [3 ]
Kieffer, Brigitte L. [2 ]
Freund-Mercier, Marie Jose [1 ]
Barrot, Michel [1 ]
机构
[1] Univ Strasbourg, CNRS, Inst Neurosci Cellulaires & Integrat, F-67084 Strasbourg, France
[2] Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France
[3] Hop Univ, Ctr Douleur, Strasbourg, France
关键词
analgesia; antidepressants; chronic; mice; opioid; transgenic;
D O I
10.1016/j.biopsych.2007.06.016
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: The therapeutic effect of antidepressant drugs against depression usually necessitates a chronic treatment. A large body of clinical evidence indicates that antidepressant drugs can also be highly effective against chronic neuropathic pain. However, the mechanism by which these drugs alleviate pain is still unclear. Methods: We used a murine model of neuropathic pain induced by sciatic nerve constriction to study the antiallodynic properties of a chronic treatment with the tricyclic antidepressants nortriptyline and amitriptyline. Using knockout and pharmacological approaches in mice, we determined the influence of delta-opioid receptors in the therapeutic action of chronic antidepressant treatment. Results: In our model, a chronic treatment by tricyclic antidepressant drugs totally suppresses the mechanical allodynia in neuropathic C57BI/6J mice. This therapeutic effect can be acutely reversed by an injection of the delta-opioid receptor antagonist naltrindole. Moreover, the antiallodynic property of antidepressant treatment is absent in mice deficient for the delta-opioid receptor gene. Conclusions: The antiallodynic effect of chronic antidepressant treatment is mediated by a recruitment of the endogenous opioid system acting through delta-opioid receptors.
引用
收藏
页码:633 / 636
页数:4
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