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OtherANALGESIA AND DRUGS OF ABUSE

Evaluation of Gabapentin and S-(+)-3-Isobutylgaba in a Rat Model of Postoperative Pain

Mark J. Field, Elizabeth F. Holloman, Scott McCleary, John Hughes and Lakhbir Singh
Journal of Pharmacology and Experimental Therapeutics September 1997, 282 (3) 1242-1246;
Mark J. Field
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Elizabeth F. Holloman
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Scott McCleary
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John Hughes
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Lakhbir Singh
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Abstract

Gabapentin and S-(+)-3-isobutylgaba are anticonvulsant agents that selectively interact with the α2δ subunit of voltage-dependent calcium channels. This report describes the activities of these two compounds in a rat model of postoperative pain. An incision of the plantaris muscle of a hind paw induced thermal hyperalgesia and tactile allodynia lasting at least 3 days. Postoperative testing was carried out using the plantar test for thermal hyperalgesia and von Frey hairs for tactile allodynia. A single s.c. dose of gabapentin, 1 h before surgery, dose-dependently (3–30 mg/kg) blocked the development of allodynia and hyperalgesia with a minimum effective dose (MED) of 10 and 30 mg/kg, respectively. The highest dose of gabapentin prevented development of hyperalgesia and allodynia for 24 and 49 h, respectively. Similar administration of S-(+)-3-isobutylgaba also dose-dependently (3–30 mg/kg, s.c.) prevented development of hyperalgesia and allodynia with MED of 3 and 10 mg/kg, respectively. The highest dose ofS-(+)-3-isobutylgaba completely blocked development of both nociceptive responses for 3 days. The administration ofS-(+)-3-isobutylgaba (30 mg/kg s.c.) 1 h after surgery also completely blocked the maintenance of hyperalgesia and allodynia, but its duration of action was much shorter (3 h). The administration of morphine (1–6 mg/kg s.c.) 0.5 h before surgery prevented the development of thermal hyperalgesia with a MED of 1 mg/kg. However, unlike gabapentin and S-(+)-3-isobutylgaba, it had little effect on the development of tactile allodynia. It is suggested that gabapentin and S-(+)-3-isobutylgaba may be effective in the treatment of postoperative pain.

Footnotes

  • Send reprint requests to: Dr L. Singh, Department of Biology, Parke-Davis Neuroscience Research Centre, Cambridge University Forvie Site, Robinson Way, Cambridge, CB2 2QB, United Kingdom.

  • Abbreviations:
    PWL
    paw withdrawal latency
    MED
    minimum effective dose
    GABA
    γ-aminobutyric acid
    S.E.M.
    standard error of the mean
    ANOVA
    analysis of variance
    s.c.
    subcutaneous
    • Received February 10, 1997.
    • Accepted May 8, 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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OtherANALGESIA AND DRUGS OF ABUSE

Evaluation of Gabapentin and S-(+)-3-Isobutylgaba in a Rat Model of Postoperative Pain

Mark J. Field, Elizabeth F. Holloman, Scott McCleary, John Hughes and Lakhbir Singh
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1242-1246;

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OtherANALGESIA AND DRUGS OF ABUSE

Evaluation of Gabapentin and S-(+)-3-Isobutylgaba in a Rat Model of Postoperative Pain

Mark J. Field, Elizabeth F. Holloman, Scott McCleary, John Hughes and Lakhbir Singh
Journal of Pharmacology and Experimental Therapeutics September 1, 1997, 282 (3) 1242-1246;
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