κ-Opioid receptors are not necessary for the antidepressant treatment of neuropathic pain.
Title | κ-Opioid receptors are not necessary for the antidepressant treatment of neuropathic pain. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Megat S, Bohren Y, Doridot S, Gaveriaux-Ruff C, Kieffer BL, Freund-Mercier M-J, Yalcin I, Barrot M |
Journal | Br J Pharmacol |
Volume | 172 |
Issue | 4 |
Pagination | 1034-44 |
Date Published | 2015 Feb |
ISSN | 1476-5381 |
Abstract | BACKGROUND AND PURPOSE: Tricyclic antidepressants are used clinically as first-line treatments for neuropathic pain. Opioid receptors participate in this pain-relieving action, and preclinical studies in receptor-deficient mice have highlighted a critical role for δ-, but not μ-opioid receptors. In this study, we investigated whether κ-opioid (KOP) receptors have a role in the antiallodynic action of tricyclic antidepressants.EXPERIMENTAL APPROACH: We used a model of neuropathic pain induced by unilateral sciatic nerve cuffing. In this model, the mechanical allodynia was evaluated using von Frey filaments. Experiments were conducted in C57BL/6J mice, and in KOP receptor-deficient mice and their wild-type littermates. The tricyclic antidepressant nortriptyline (5 mg · kg(-1)) was delivered twice a day for over 2 weeks. Agonists and antagonists of opioid receptors were used to test the selectivity of the KOP receptor antagonist norbinaltorphimine (nor-BNI) in mice with neuropathic pain.KEY RESULTS: After 12 days of treatment, nortriptyline relieved neuropathic allodynia in both wild-type and KOP receptor-deficient mice. Surprisingly, acute nor-BNI reversed the effect of nortriptyline in both wild-type and KOP receptor-deficient mice. Further experiments showed that nor-BNI action was selective for KOP receptors at a late time-point after its administration (8 h), but not at an early time-point, when it may also interact with δ-opioid (DOP) receptors.CONCLUSIONS AND IMPLICATIONS: KOP receptors are not necessary for the effect of a tricyclic antidepressant against neuropathic allodynia. These findings together with previous data indicate that the DOP receptor is the only opioid receptor that is necessary for the antiallodynic action of antidepressants. |
DOI | 10.1111/bph.12963 |
Alternate Journal | Br. J. Pharmacol. |
PubMed ID | 25297905 |
PubMed Central ID | PMC4314193 |