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.