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

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Benbouzid M, Gaveriaux-Ruff C, Yalcin I, Waltisperger E, Tessier LH, Muller A, Kieffer BL, Freund-Mercier MJ, Barrot M

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

Biol Psychiatry. 2008 Mar 15;63(6):633-6. doi: 10.1016/j.biopsych.2007.06.016. Epub 2007 Aug 13.

PubMed ID

17693391 [ View in PubMed

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Abstract

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 C57Bl/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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Amitriptyline	Delta-type opioid receptor	Protein	Humans	Unknown	Agonist	Details