Involvement of δ1-opioid receptors in the antinociceptive effects of mexiletine in mice

Abstract

The mechanisms of the antinociceptive effect of mexiletine were assessed by administering selective μ-, δ- and ϰ-opioid receptor antagonists in diabetic and non-diabetic mice. Intraperitoncal administration of mexiletine, at doses of 10 and 30 mg/kg, produced dose-dependent antinociception in the tail-pinch test in both non-diabetic and diabetic mice. The antinociceptive effect of mexiletine in diabetic mice was significantly greater than that in non-diabetic mice. The antinociceptive effect of mexiletine did not result from the activation of μ- or ϰ-opioid receptors in either non-diabetic or diabetic mice, since treatment with either β-funaltrexamine, a selective μ-opioid receptor antagonist, or nor-binaltorphimine, a selective ϰ-opioid receptor antagonist, was ineffective in blocking mexiletineinduced antinociception. The antinociceptive effect of mexiletine was significantly antagonized by naltrindole, a selective δ-opioid receptor antagonist, in both non-diabetic and diabetic mice. Furthermore, the antinociceptive effect of mexiletine was significantly reduced in both non-diabetic and diabetic mice following pretreatment with 7-benzylidenenaltrexone, a selective δ 1-opioid receptor antagonist, but not with naltriben, a selective δ 2-opioid receptor antagonist. These results suggest that δ 1-opioid receptor-mediated mechanisms may be involved in the antinociceptive effect of mexiletine.