Differential mechanisms mediating beta-endorphin- and morphine-induced analgesia in mice.
Effects of yohimbine, methysergide and naloxone given intrathecally (i.t.) and naloxone given intracerebroventricularly (i.c.v.) on inhibition of the tail-flick and hot-plate response induced by beta-endorphin and morphine given i.c.v. were studied in male ICR mice. Yohimbine (1.5 and 15 micrograms) and methysergide (1.5 and 15 micrograms) injected i.t. antagonized inhibition of the tail-flick response induced by morphine but not beta-endorphin administered i.c.v. On the other hand, naloxone (20 ng) injected i.t. antagonized inhibition of the tail-flick response induced by i.c.v. administered beta-endorphin but not morphine. Yohimbine and methysergide given i.t. did not antagonize inhibition of the hot-plate response induced by morphine nor did naloxone given i.t. antagonized i.c.v. beta-endorphin-induced inhibition of the hot-plate response. Naloxone given i.c.v. was more effective in antagonizing morphine-induced inhibition of the tail-flick and hot-plate response than inhibition induced by beta-endorphin given i.c.v. Naloxone at doses (0.1 and 1 microgram) which effectively reversed inhibition of the tail-flick response to i.c.v. morphine was not effective in reversing the i.c.v. beta-endorphin-induced inhibition of the tail-flick response. Our results indicate that beta-endorphin and morphine produce analgesia by stimulating separate types of opioid receptors, epsilon- for for beta-endorphin and mu- for morphine, and activate separate descending pain modulatory control systems. The supraspinal epsilon system stimulated by beta-endorphin is mediated by activation of spinal opioid receptors whereas the supraspinal mu system stimulated by morphine is mediated by activation of spinal alpha 2-adrenoceptors and serotonin receptors for the production of analgesia.
Suh
H H
HH
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Fujimoto
J M
JM
Tseng
L L
LL
D000698:Analgesia; D000818:Animals; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology; D001615:beta-Endorphin / Q000008:administration & dosage / Q000494:pharmacology*
D015016:Yohimbine; D009270:Naloxone; D001615:beta-Endorphin; D009020:Morphine; D008784:Methysergide