Analgesia mediated by spinal kappa-opioid receptors.

The results from 44 experiments performed on 13 rats with chronically implanted lumbar subarachnoid catheters are reported. ICI 197 067 produced dose-dependent segmental analgesic effects when measurement of electrical current threshold for pain was used as the nociceptive test. Ten microliters of intrathecal ICI 197 067 (0.06 mg ml-1; 1.5 nmol) caused a significant rise in the current threshold for pain in the tail of 1.56 +/- 0.04 x control (mean +/- SEM) but no significant change in pain threshold in the neck (1.03 +/- 0.03 x control). By contrast, simultaneous measurements of tail-flick latency in these animals revealed no significant rise in pain thresholds using this nociceptive test. Intraperitoneally administered naloxone produced a dose-dependent suppression of the spinally mediated analgesic effect produced by ICI 197 067; the ED50 for this effect was 0.79 mumol kg-1, a value very close to the ED50 for naloxone antagonism of ketocyclazocine spinally mediated analgesia. We conclude that ICI 197 067 produces spinally mediated analgesia by binding to spinal-cord kappa-opioid receptors.