Intrathecal endomorphin-1 produces antinociceptive activities modulated by alpha 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 opioid ligand, shows the greatest selectivity and affinity for the mu-opiate receptor 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, tail pressure and formalin tests. Intrathecal endomorphin-1; produced dose-dependent antinociceptive effects in the three tests. ED50 (CI95) values for antinociception of i.t. endomorphin-1 in the tail flick test and tail pressure test were 1.9 (0.96-3.76) nmol and 1.8 (0.8-4.2) nmol, respectively. ED50 (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. beta funaltrexamine (a mu-opioid receptor selective antagonist) Significantly antagonized the antinociceptive effects of endomorphin-1 in the three tests. Beta-funaltrexamine alone had not effects an the three tests. The antinociceptive effects of endomorphin-1 were also antagonized by i.t, yohimbine tan alpha 2-adrenoceptor selective antagonist). The combination of ineffective doses of i.t, clonidine tan alpha 2-adrenoceptor agonist):and endomorphin-1 produced a significant antinociception in the three tests. The results showed that intrathecal endomorphin-1 produced antinociception in a dose-dependent manner in the rat tail flick, tail pressure and formalin tests, which was mediated by spinal mu-opioid receptors and modulated by alpha 2-adrenoceptors. (C) 2000 Elsevier Science Inc.