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Anesth Analg 2008; 106:1897-1903
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318172b993
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ANALGESIA

The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model

Radica M. Stepanovic-Petrovic, BPharm, PhD*, Maja A. Tomic, BPharm, MSc*, Sonja M. Vuckovic, MD, PhD{dagger}, Sonja Paranos, BPharm*, Nenad D. Ugresic, BPharm, PhD*, Milica S. Prostran, MD, PhD{dagger}, Slobodan Milovanovic, MD, PhD{ddagger}, and Bogdan Boskovic, BPharm, MD, PhD{ddagger}

From the *Department of Pharmacology, Faculty of Pharmacy, {dagger}Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, and {ddagger}Military Medical Academy, Belgrade, Serbia.

Address correspondence and reprint requests to Radica M. Stepanovic-Petrovic, BPharm, PhD, Department of Pharmacology, Faculty of Pharmacy, Vojvode Stepe 450, POB 146, 11221 Belgrade, Serbia. Address e-mail to racabbr{at}eunet.yu.

Abstract

BACKGROUND: There is evidence supporting the antinociceptive effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in various models of neuropathic pain as well as inflammatory somatic pain. Data are lacking on the antinociceptive potential of these drugs against visceral pain. In this study, we examined and compared the effects of carbamazepine, oxcarbazepine, gabapentin, and topiramate in the writhing test as a visceral pain model in the mouse. In addition, the influence of these anticonvulsants on motor performance was examined to compare the tolerability of these anticonvulsants when used against acute visceral pain.

METHODS: The antinociceptive effects of these anticonvulsants were examined in the acetic acid writhing test in mice. The side effect propensity of these drugs was examined using the rotarod test.

RESULTS: Carbamazepine (25–60 mg/kg; p.o.), oxcarbazepine (10–40 mg/kg; p.o.), gabapentin (10–70 mg/kg; p.o.), and topiramate (5–30 mg/kg; p.o.) caused a significant dose-dependent reduction the number of writhes in the writhing test. In the rotarod test, carbamazepine (60–140 mg/kg; p.o.) and oxcarbazepine (120–450 mg/kg; p.o.) significantly reduced the time spent on the rotarod in a dose- and time-dependent manner. Gabapentin (1000–2000 mg/kg; p.o.) and topiramate (400–1500 mg/kg; p.o.) did not produce significant impairment of motor performance at the highest doses used. The therapeutic index (motor impairing dose TD50/writhing ED50) values were topiramate (>148.5) > gabapentin (>60.2) > oxcarbazepine (15.2) > carbamazepine (2.3).

CONCLUSIONS: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.






Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2008 by the International Anesthesia Research Society.