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OtherANALGESIA AND DRUGS OF ABUSE

Antinociceptive Properties of Propofol: Involvement of Spinal Cord γ-Aminobutyric AcidA Receptors

R. Nadeson and C. S. Goodchild
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1181-1186;
R. Nadeson
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C. S. Goodchild
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Abstract

In this study, we investigated the interaction of propofol (a compound used widely as an intravenous anesthetic) with γ-aminobutyric acidA (GABAA) anddelta 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 GABAA 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 GABAA receptors. This combination leads to activation of a spinal cord system involving adelta opioid receptor; the same mechanisms involved with midazolam-induced spinal antinociception.

Footnotes

  • Send reprint requests to: Prof. C. S. Goodchild, Monash University, Department of Anaesthesia, Monash Medical Centre, 246 Clayton Rd., Clayton, Victoria, Australia 3168.

  • Abbreviations:
    ECT
    electrical current threshold test
    GABA
    γ-aminobutyric acid
    i.p.
    intraperitoneal
    i.t.
    intrathecal
    TFL
    tail-flick latency
    %MPE
    percentage of the maximal possible effect
    • Received February 4, 1997.
    • Accepted May 5, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 3
1 Sep 1997
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Antinociceptive Properties of Propofol: Involvement of Spinal Cord γ-Aminobutyric AcidA Receptors

R. Nadeson and C. S. Goodchild
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1181-1186;

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OtherANALGESIA AND DRUGS OF ABUSE

Antinociceptive Properties of Propofol: Involvement of Spinal Cord γ-Aminobutyric AcidA Receptors

R. Nadeson and C. S. Goodchild
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1181-1186;
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