Comparisons of descending pain inhibitory pathways activated by beta-endorphin and morphine as characterized by supraspinal and spinal antinociceptive interactions in mice.
Morphine administered concurrently by i.c.v. plus intrathecal (i.t.) injection produces a multiplicative (synergistic) interaction for antinociception in the tail-flick test. Inasmuch as i.c.v. administered beta-endorphin has been proposed to produce antinociception by activating a descending pain inhibitory system different from that activated by morphine, the present experiments compared the two systems in mice. The responses to i.c.v., i.t. and combinations of i.c.v. plus i.t. administration of morphine and beta-endorphin were evaluated by determination of ED50 values which were plotted as isobolograms and compared to calculated theoretical additive ED50 values. The following combinations gave additive interactions: i.c.v. plus i.t. beta-endorphin, i.c.v. beta-endorphin plus i.t. morphine and i.t. morphine plus i.t. beta-endorphin. These results were consistent with the hypothesis that i.c.v. beta-endorphin stimulates supraspinal epsilon receptors which activate a descending pathway involving enkephalinergic neuronal mediation and spinal postsynaptic mu receptors. Stimulation of these mu receptors by i.t. morphine or i.t. beta-endorphin together with the supraspinal effect of beta-endorphin resulted in an additive interaction. Multiplicative interactions were obtained for the following combinations: i.c.v. morphine plus i.t. morphine, i.c.v. morphine plus i.t. beta-endorphin and i.c.v. morphine plus i.c.v. beta-endorphin. Morphine administered i.c.v. stimulated supraspinal mu receptors to activate a descending pain inhibitory pathway which is mediated spinally by monoamines. The i.t. agonists in this case activated the spinal mu receptor which is presumed to be part of the beta-endorphin descending pathway described above. Thus, when both pathways were activated simultaneously the interaction was multiplicative.(ABSTRACT TRUNCATED AT 250 WORDS)
Roerig
S C
SC
Research Service, Veterans Administration Medical Center, Milwaukee, Wisconsin.
Fujimoto
J M
JM
Tseng
L F
LF
D000698:Analgesia; D000818:Animals; D004361:Drug Tolerance; D004525:Efferent Pathways / Q000187:drug effects; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D013116:Spinal Cord / Q000187:drug effects*; D001615:beta-Endorphin / Q000494:pharmacology*
D009271:Naltrexone; D001615:beta-Endorphin; C024524:beta-funaltrexamine; D009020:Morphine