title: Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2.
abstract: Two highly-selective mu-opioid receptor agonists, endomorphin-1 and -2, were recently purified from bovine brain and are postulated to be endogenous mu-opioid receptor ligands. We sought to determine the effects of these ligands at the spinal level in mice. Endomorphin-1 and -2 produced short acting, naloxone-sensitive antinociception in the tail flick test and inhibited the behavior elicited by intrathecally injected substance P. Both endomorphin-1 and -2 were anti-allodynic in the dynorphin-induced allodynia model. Although acute tolerance against both endomorphins developed rapidly, endomorphin-1 required a longer pretreatment time before tolerance was observed. We conclude that the endomorphins are potent spinal antinociceptive and anti-allodynic agents and that they or related compounds may prove therapeutically useful as spinal analgesics.
authors.affiliation: Graduate Program in Neuroscience, University of Minnesota, Minneapolis 55455, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Stone
authors.forename: C A
authors.initials: CA
authors.lastname: Fairbanks
authors.forename: T M
authors.initials: TM
authors.lastname: Laughlin
authors.forename: H O
authors.initials: HO
authors.lastname: Nguyen
authors.forename: T M
authors.initials: TM
authors.lastname: Bushy
authors.forename: M W
authors.initials: MW
authors.lastname: Wessendorf
authors.forename: G L
authors.initials: GL
authors.lastname: Wilcox
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D004361:Drug Tolerance; D006358:Hot Temperature; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000494:pharmacology*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013373:Substance P / Q000037:antagonists & inhibitors
chemical_list: D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D013373:Substance P; C105294:endomorphin 2