Met]enkephalin in the spinal cord is involved in the antinociception induced by intracerebroventricularly-administered etorphine in the mouse

Abstract

We have recently reported that the antinociception induced by etorphine given i.c.v. is mediated in part by the stimulation of both μ- and ϵ-opioid receptors and the activation of both monoaminergic and opioidergic descending pain control systems. [29]Since the opioid ϵ-receptor-mediated antinociception induced by β-endorphin is mediated by the release of [Met]enkephalin and subsequent stimulation of δ-opioid receptors in the spinal cord, the present studies were designed to determine if β-endorphin-like action is also involved in etorphine-induced antinociception. The tail-flick test was used to assess the antinociceptive response performed in male ICR mice. Etorphine at doses from 5–20 ng given i.c.v. produced a dose-dependent inhibition of the tail-flick response. The inhibition of the tail-flick response induced by etorphine given i.c.v. was antagonized by intrathecal pretreatment for 60 min with antiserum against [Met]enkephalin (10 μg), but not with antiserum against [Leu]enkephalin (10 μg) or dynorphin A (1–13) (10 μg). Desensitization of δ-opioid receptors in the spinal cord by intrathecal pretreatment with [Met]enkephalin (5 μg) for 60 min attenuated i.c.v. administered etorphine-induced tail-flick inhibition. However, intrathecal pretreatment with [Leu]enkephalin (5 μg) or dynorphin A (1–17) (0.1 μg) for 60 min did not attenuate i.c.v. administered etorphine-induced tail-flick inhibition. The results indicate that antinociception induced by etorphine given i.c.v. is mediated in part by the stimulation of the ϵ-opioid receptor at the supraspinal sites and by the release of [Met]enkephalin which subsequently stimulates δ-opioid receptors in the spinal cord.