δ-Opioid receptor agonist SNC80 induces central antinociception mediated by Ca2+-activated Cl- channels

Abstract

Objectives The aim of this study was to determine whether Ca 2+-activated Cl- channels (CaCCs) are involved in central antinociception induced by the activation of μ-, δ- and κ-opioid receptors. Methods The nociceptive threshold for thermal stimulation was measured using the tail-flick test in Swiss mice. The drugs were administered via the intracerebroventricular route. Probabilities values of P < 0.05 were considered to be statistically significant (analysis of variance/Bonferroni test). Key findings The results demonstrate that exposure to the CaCC blocker niflumic acid (2, 4 and 8 μg) partially reverses the central antinociception induced by the δ-opioid receptor agonist SNC80 ((+)-4-[(αR)-α- ((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N, N-diethylbenzamide; 4 μg). In contrast, niflumic acid did not modify the antinociceptive effect of the μ-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (0.5 μg) or κ-opioid receptor agonist bremazocine (4 μg). Conclusions These data provide evidence for the involvement of CaCCs in δ-opioid receptor-induced central antinociception resulting from receptor activation by the agonist SNC80. CaCC activation does not appear to be involved when μ- and κ-opioid receptors are activated. © 2012 Royal Pharmaceutical Society.