PoSSible invOIVement Of u1~OpiOid receptOrS in the fentanyl- Or mOrphine-induced antinOCiceptiOn at SupraSpinal and Spinal SiteS

Fentanyl has been shown to be a potent analgesic with a lower propensity to produce tolerance and physical dependence in the clinical setting. The present study was designed to investigate the mechanisms of fentanylor morphine-induced antinociception at both supraspinal and spinal sites. In the mouse tail-flick test, the antinociceptive effects induced by both fentanyl and morphine were blocked by either the u I -opioid receptor antagonist naloxonazine or the u1/u2-0pioid receptor antagonist ~-funaltrexamine (~-FNA) afier s.c,, i,c.v. or i,t. injection. In contrast, both fentanyl and morphine given i,c.v. or i.t. failed to produce antinociception in u1-deficient CXBK mice. These findings indicate that like morphine, the antinociception induced by fentanyl may be mediated predominantly through rllopioid receptors at both supraspinal and spinal sites in mice. We also determined the ED50 Values for s.c.-, i.c,v.and i.t.-administered fentanylor morphine-induced antinociception in mice. The ED50 values for s,c.-, i,c.v.and i.t.-administered fentanyl-induced antinociception were 73.7, 18,5 and 1.2-fold lower than that of morphine, respectively. The present data clearly suggest the usefulness of peripheral treatment with fentanyl for the control ofpain, C 2002 Elsevier Science Inc. All rights reserved.