Antinociceptive properties of propofol: involvement of spinal cord gamma-aminobutyric acid(A) receptors.
In this study, we investigated the interaction of propofol (a compound used widely as an intravenous anesthetic) with gamma-aminobutyric acid(A) (GABA(A)) and delta opioid receptors at the level of the spinal cord. Nociceptive thresholds were measured in rats through the use of electrical current testing (ECT) and tail-flick latency. Full recovery from sedation occurred 36.3 +/- 1.7 min (mean +/- S.E.M.; n = 20) after 40 mg/kg propofol i.p. Forty minutes after administration, there was residual antinociception when assessed by ECT but not when assessed by noxious heat. The ECT antinociceptive effects of propofol at tail but not neck sites were suppressed by intrathecal injection of the GABA(A) antagonists bicuculline and SR-95531 and the delta opioid antagonist naltrindole. These results suggest that there is an interaction between propofol and antagonists at receptors in the caudal segments of the spinal cord responsible for tail innervation. Antagonist dose-response curves were compared with those for suppression of intrathecal midazolam-induced antinociception. All intrathecal antagonists reversed the antinociceptive effect of propofol with the same dose-response curves as those previously obtained for suppression of the effect of intrathecal midazolam. We conclude that propofol, when given intraperitoneally, produces antinociception in rats through an interaction with spinal GABA(A) receptors. This combination leads to activation of a spinal cord system involving a delta opioid receptor; the same mechanisms involved with midazolam-induced spinal antinociception.
Nadeson
R
R
Monash University, Department of Anesthesia, Monash Medical Centre, Clayton, Victoria, Australia.
Goodchild
C S
CS
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*
D018712:Analgesics, Non-Narcotic; D018686:Anesthetics, Intravenous; D011963:Receptors, GABA-A; D015742:Propofol