Differential involvement of mu-opioid receptor subtypes in endomorphin-1-and-2-induced antinociception

We investigated the role of mu-opioid receptor subtypes in both endomorphin -1 and endomorphin-2 induced antinociception in mice using supraspinally me diated behavior. With tail pressure as a mechanical noxious stimulus, both intracerebroventricularly (i.c.v.) and intrathecally (i.t.) injected-endomo rphins produced potent and significant antinociceptive activity. Antinocice ption induced by i.t. and i.c.v. injection of endomorphin-1 was not reverse d by pretreatment with a selective mu(1)-opioid receptor antagonist, naloxo nazine (35 mg/kg, s.c.). By contrast, antinociception induced by i.t. and i .c.v. endomorphin-2 was significantly decreased by mu(1)-opioid receptor an tagonist. Antinociception of both i.t. and i.c.v. endomorphin-1 and -2 was completely reversed by pretreatment with beta-funaltrexamine (40 mg/kg, s.c .). The results indicate that endomorphins may produce antinociception thro ugh the distinct mu(1) and mu(2) subtypes of mu-opioid receptor. (C) 1999 E lsevier Science B.V. All rights reserved.