Spinal analgesic actions of the new endogenous opioid peptides endomorphin-1 and -2.
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.
Stone
L S
LS
Graduate Program in Neuroscience, University of Minnesota, Minneapolis 55455, USA.
Fairbanks
C A
CA
Laughlin
T M
TM
Nguyen
H O
HO
Bushy
T M
TM
Wessendorf
M W
MW
Wilcox
G L
GL
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
D000701:Analgesics, Opioid; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; D013373:Substance P; C105294:endomorphin 2