Intrathecal beta-funaltrexamine antagonizes intracerebroventricular beta-endorphin- but not morphine-induced analgesia in mice.
We have reported previously that beta-endorphin and morphine administered supraspinally produce analgesia by activating different descending pain inhibitory systems in rats. The descending system activated by beta-endorphin involves a spinal endorphinergic system whereas the descending system activated by morphine does not. To determine if this differential action of intraventricular beta-endorphin and morphine also occurs in mice, the effects of pretreatment with intrathecal (i.t.) and i.c.v. beta-funaltrexamine (beta-FNA) on analgesic response induced by i.c.v. and i.t. beta-endorphin and morphine were studied in mice. beta-FNA (2.5 micrograms) was injected i.t. or i.c.v. 24 hr before beta-endorphin or morphine administration and hot-plate and tail-flick responses were measured. Intrathecal beta-FNA attenuated i.c.v. beta-endorphin- but not i.c.v. morphine-induced analgesia. On the other hand, i.t. beta-FNA blocked both i.t. beta-endorphin- and morphine-induced analgesia, but was more effective in blocking the effects of i.t. morphine than beta-endorphin. At the supraspinal sites, beta-FNA administered i.c.v. was found to antagonize i.c.v. morphine-induced analgesia but not i.c.v. beta-endorphin-induced analgesia. The present results in mice are consistent with previous studies in rats and indicate that beta-endorphin and morphine activate different supraspinal opioid receptors. Also, analgesia produced by these two opioids resulted from activation of different descending pain inhibitory systems. The spinal endorphinergic system was involved in the production of i.c.v. beta-endorphin-, but not morphine-induced analgesia.
Suh
H H
HH
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Tseng
L F
LF
D000698:Analgesia; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008959:Models, Neurological; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D001615:beta-Endorphin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D009292:Narcotic Antagonists; D009271:Naltrexone; D001615:beta-Endorphin; C024524:beta-funaltrexamine; D009020:Morphine