Contribution of spinal mu1-opioid receptors to morphine-induced antinociception.
To determine the role of mu-opioid receptor subtypes, mu1 and mu2, in antinociception induced by intrathecal (i.t.) or intracerebroventricular (i.c.v.) injection of morphine, we assessed the effect of naloxonazine, a selective antagonist at mu1-opioid receptors. The antinociceptive effects of morphine were measured using four different nociceptive tests. The selective mu1 antagonist, naloxonazine (35 mg/kg, s.c.), 24 h before testing antagonized the antinociceptive effect of morphine on responses to chemical and thermal stimuli to a greater extent than that on responses to mechanical stimuli, as judged from ED50 values. The present results suggest that the antinociceptive activity of both i.t. and i.c.v. morphine on responses to chemical and thermal stimuli may be mediated through the mu1-opioid receptor subtype (naloxonazine-sensitive sites). These findings may be interpreted as indicative of the existence of mu1-receptor subtypes capable of mediating antinociception not only in supraspinal sites but also in spinal sites.
Sato
T
T
Department of Pharmaceutics, Tohoku College of Pharmacy, Sendai, Japan.
Sakurada
S
S
Takahashi
N
N
Sakurada
T
T
Tan-No
K
K
Wako
K
K
Kisara
K
K
D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004347:Drug Interactions; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010147:Pain Measurement; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000145:classification / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology*
D000700:Analgesics; D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; D009020:Morphine; C034643:naloxonazine