Abstract
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 (i.t.) in the rat tail flick, tail pressure and formalin tests. Intrathecal endomorphin-1 produced dose-dependent antinociceptive effects in the three tests ED
50 (CI
95) 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 ED
50. (CI
95) 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 on the three tests. The antinociceptive effects of endomorphin-1 were also antagonized by i.t. yohimbine (an alpha 2-adrenoceptor selective antagonist). The combination of ineffective doses of i.t. clonidine (an 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.
