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.
Goodchild
C S
CS
Department of Anaesthesia, University of Leeds, United Kingdom.
Sanghera
S
S
Serrao
J M
JM
Gent
J P
JP
D015360:Analgesia, Epidural; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects* / Q000502:physiology; D012684:Sensory Thresholds / Q000187:drug effects; D013997:Time Factors
D009294:Narcotics; D011759:Pyrrolidines; D011957:Receptors, Opioid; C058467:ICI 197067; D009270:Naloxone