Intrathecal endomorphin-1 produces antinociceptive activities modulated byalpha 2-adrenoceptors in the rat tail flick, tail pressure and formalin tests

It is known that spinal morphine produces antinociception that is modulated by alpha 2-adrenoceptors. Endomorphin-1, a newly-isolated endogenous opioi d ligand, shows the greatest selectivity and affinity for the mu-opiate rec eptor of any endogenous substance found to date and may serve as a natural ligand for the mu-opiate receptor. We examined the antinociceptive effects of endomorphin-1 administered intrathecally tit) in the rat tail flick, tai l pressure and formalin tests. Intrathecal endomorphin-1; produced dose-dep endent antinociceptive effects in the three tests. ED50 (CI95) values for a ntinociception of i.t. endomorphin-1 in the tail flick test and tail pressu re test were 1.9 (0.96-3.76) nmol and 1.8 (0.8-4.2) nmol, respectively. ED5 0 (CI95) values For phase 1 and phase 2 in the formalin test were 12.5 (7.9 -19.8) nmol and 17.5 (10.2-30) nmol, respectively. Pretreatment with i.t. b eta funaltrexamine (a mu-opioid receptor selective antagonist) Significantl y antagonized the antinociceptive effects of endomorphin-1 in the three tes ts. Beta-funaltrexamine alone had not effects an the three tests. The antin ociceptive effects of endomorphin-1 were also antagonized by i.t, yohimbine tan alpha 2-adrenoceptor selective antagonist). The combination of ineffec tive doses of i.t, clonidine tan alpha 2-adrenoceptor agonist):and endomorp hin-1 produced a significant antinociception in the three tests. The result s showed that intrathecal endomorphin-1 produced antinociception in a dose- dependent manner in the rat tail flick, tail pressure and formalin tests, w hich was mediated by spinal mu-opioid receptors and modulated by alpha 2-ad renoceptors. (C) 2000 Elsevier Science Inc.