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

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-Ala(2), N-Me-Phe(4), Gly(5)-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.