Analgesic effects of mu-, delta- and kappa-opiate agonists and, in particular, dynorphin at the spinal level.
To investigate the role of multiple opiate receptors in spinal mechanisms of antinociception the activity of various opiate receptor agonists was determined against different nociceptive stimuli in the mouse and rat. Intrathecal administration of the putative kappa-receptor agonists dynorphin A (DYN), bremazocine, and ethylketocyclazocine, as well as the delta-agonist D-Ala2,D-Leu5-enkephalin and the mu-agonists, Tyr-D-Ala-Gly-MePhe-NH-(CH2)2OH and morphine resulted in a dose-dependent antinociceptive effect. The order of potencies was similar for visceral and thermal pain. Inhibition of writhing in mice was much more strongly antagonized by MR 2266 than by naloxone, and des-Tyr1-DYN1-13 was 50 times less potent than DYN in this test suggesting that DYN acts through the kappa-receptor. It is concluded that mu-, delta- and kappa-opiate receptors are involved in spinally mediated antinociception related to kinds of noxious stimuli.
D000818:Animals; D004399:Dynorphins; D004723:Endorphins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009294:Narcotics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D004723:Endorphins; D009294:Narcotics; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004399:Dynorphins