Spinally mediated antinociception following intrathecal chlordiazepoxide--further evidence for a benzodiazepine spinal analgesic effect.
This is a report of the results of 25 experiments in five rats investigating the dose-response relationship for the antinociceptive effects of chlordiazepoxide given intrathecally in the dose range 0.03-0.9 mumol and a further 40 experiments in eight rats investigating the actions of flumazenil and naloxone on this effect. Electrical-current thresholds for pain were measured in the skin of the tail and neck of rats with previously implanted lumbar subarachnoid catheters. Intrathecal chlordiazepoxide produced spinally mediated antinociception, i.e. rises in the current threshold for pain in the tail without a significant change in the neck. This antinociceptive effect was dose dependent. Flumazenil 16.5 mumol kg-1 i.p. reduced the response caused by chlordiazepoxide 0.6 mumol by 78 +/- 6% (mean +/- SEM). By contrast, the same dose of flumazenil did not significantly affect the antinociceptive effect of an equipotent dose of intrathecal fentanyl 0.74 nmol. Naloxone 0.38 mumol kg-1 i.p. abolished the spinally mediated antinociception caused by fentanyl (96 +/- 7% suppression) but did not significantly reduce the effect of chlordiazepoxide (27 +/- 13% suppression). However, a higher dose of naloxone (6.1 mumol kg-1 i.p.) caused significant partial suppression (79 +/- 10.7%) of chlordiazepoxide spinal antinociception. We conclude that chlordiazepoxide produces an antinociceptive effect by combination with benzodiazepine receptors in the spinal cord.
Boulter
N
N
Department of Pharmacology, University of Leeds, United Kingdom.
Serrao
J M
JM
Gent
J P
JP
Goodchild
C S
CS
D015360:Analgesia, Epidural; D000818:Animals; D002408:Catheters, Indwelling; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology; D005442:Flumazenil / Q000008:administration & dosage / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D012684:Sensory Thresholds / Q000187:drug effects
D011963:Receptors, GABA-A; D009270:Naloxone; D005442:Flumazenil; D002707:Chlordiazepoxide; D005283:Fentanyl