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ANALGESIA

Levetiracetam Reduces Anesthetic-Induced Hyperalgesia in Rats

David P. Archer, MD, MSc^*, Yves Lamberty, PhD, Bing Wang, MD, MSc^*, Melinda J. Davis, MD^*, Naaznin Samanani, BSc^*, and Sheldon H. Roth, PhD^*

From the Departments of *Anesthesiology, Clinical Neurosciences, and Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, Calgary, Canada; and Preclinical CNS Research, UCB S.A., Braine-l’Alleud, Belgium.

Address correspondence to D. Archer, MD, MSc, Department of Anesthesiology, Foothills Medical Centre, 1403 29th St., NW, Calgary, Alberta, Canada T2N 2T9. Address e-mail to david.archer{at}calgaryhealthregion.ca. Reprints will not be available from the authors.

Abstract

BACKGROUND: As part of an increase in excitability, small doses of pentobarbital, propofol, and midazolam induce an increased sensitivity to pain. Specific therapy to prevent or reduce this excitability may offer advantages over current clinical management with analgesics and sedatives. The pharmacological profile of the novel antiepileptic drug, levetiracetam, suggests that it may reduce the intensity of the excitatory stages of anesthesia.

METHODS: We examined the influence of levetiracetam on the reduction of the nociceptive reflex threshold in rats by sedative doses of pentobarbital, propofol, and midazolam. Measurements of nociceptive reflex threshold to pressure and heat were made and then repeated after intraperitoneal injection of saline or one of three doses of levetiracetam (100, 200, 500 mg/kg). Pentobarbital (30 mg/kg), propofol (30 mg/kg), or midazolam (1.9 mg/kg) were then administered. The reflex threshold was measured every 10 min, starting at 5 min after the sedative injection, until 65 min had elapsed.

RESULTS: Levetiracetam did not alter nociceptive reflex threshold in nonsedated animals (P = 0.11) or influence the degree or duration of sedation. The three anesthetic/sedative drugs reduced the nociceptive reflex threshold by 20%–30% of control values. Levetiracetam reduced the hyperreflexia associated with pentobarbital and midazolam (P < 0.05), but not propofol.

CONCLUSIONS: These findings support further investigation into the role of levetiracetam in the prevention of anesthetic-induced excitability.

This article has been cited by other articles:

				D. Archer and S. Roth Anesthetics are exciting! Implications of pharmacologically-induced nociceptive hyperreflexia/Les anesthesiques, c'est excitant... Implications de l'hyperreflectivite nociceptive provoquee par pharmacologie Can J Anesth, January 1, 2008; 55(1): 6 - 10. [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999