Spinal kappa-opioid receptor-mediated antinociception is stimulus-specific.
The intrathecal injection of a variety of selective kappa-opioid receptor ligands did not result in significant inhibition of thermal nociceptive tail flick responses in rats. In contrast, these compounds dose dependently inhibited pressure nociceptive responses. Cross-tolerance studies revealed that the kappa-opioid receptor ligands tifluadom, U-50488H and dynorphin-(1-17) act upon a receptor distinguishable from the receptor through which morphine exerts its inhibition of mechanical nociceptive responses. The less selective kappa-opiate receptor ligands bremazocine and ethylketocyclazocine (EKC), however, blocked both tail flick and tail pressure nociceptive responses and their effect showed marked cross-tolerance to morphine in the tail flick nociceptive test, but not for the pressure nociceptive responses. We suggest that EKC and bremazocine act upon the spinal kappa-opioid receptor to block mechanical nociceptive responses but that the analgesic effect of EKC and bremazocine on thermal nociceptive responses is probably mediated via spinal micron- and/or delta-, and delta-opioid receptors, respectively.
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D001575:Benzomorphans / Q000494:pharmacology; D003496:Cyclazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D004361:Drug Tolerance; D004399:Dynorphins / Q000494:pharmacology; D016314:Ethylketocyclazocine; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013116:Spinal Cord / Q000502:physiology*
D000700:Analgesics; D001575:Benzomorphans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D001569:Benzodiazepines; D016314:Ethylketocyclazocine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; D009020:Morphine; C027248:bremazocine; D003496:Cyclazocine; C035470:tifluadom