title: Intrathecal endomorphin-1 produces antinociceptive activities modulated by alpha 2-adrenoceptors in the rat tail flick, tail pressure and formalin tests.
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. 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 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.
authors.affiliation: Department of Anesthesiology & Critical Care Medicine, Asahikawa Medical College, 078-8510 Japan. hao@asahikawa-med.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Hao
authors.forename: O
authors.initials: O
authors.lastname: Takahata
authors.forename: H
authors.initials: H
authors.lastname: Iwasaki
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D005557:Formaldehyde; D007278:Injections, Spinal; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000819:agonists; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D009842:Oligopeptides; D018341:Receptors, Adrenergic, alpha-2; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D005557:Formaldehyde; D015016:Yohimbine