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ANALGESIA

The Local Antinociceptive Actions of Nonsteroidal Antiinflammatory Drugs in the Mouse Radiant Heat Tail-Flick Test

Ahmet Dogrul, MD^*, S. Ezgi Gülmez, MD, M. Salih Deveci, MD, Husamettin Gul, MD, Michael H. Ossipov, PhD^||, Frank Porreca, PhD^||, and F. Cankat Tulunay, MD

From the *Department of Pharmacology, Gülhane Academy of Medicine, Etlik, Ankara, Turkey; Department of Pharmacology and Clinical Pharmacology and Headache Research Center, Medical School of Ankara University, Ankara, Turkey; Departments of Pathology, Analytic Toxicology, Gülhane Academy of Medicine, Etlik, Ankara, Turkey; and ||Department of Pharmacology, Arizona Health Sciences Center, University of Arizona, Tucson, Arizona.

Address correspondence and reprint requests to F. Cankat Tulunay, Department of Pharmacology and Clinical Pharmacology, Medical School of Ankara University, Ankara, Turkey. Address e-mail to f.cankat.tulunay{at}dialup.ankara.edu.tr.

Abstract

BACKGROUND: While many preclinical models detect the analgesic activity of nonsteroidal antiinflammatory drugs (NSAIDs), the radiant heat tail-flick response has repeatedly been insensitive to this class of drugs. As the tail-flick test involves nociceptive processing at spinal circuits with supraspinal modulation, it seems reasonable to assume that the NSAIDs should not modify strong nociceptive stimuli, since the primary site of action of NSAIDs is likely to be in the periphery.

METHODS: We injected 3–300 µg of diclofenac, dipyrone, ketorolac, lysine acetyl salicylate, and sodium salicylate intradermally into mice tails and evaluated the tail-flick response to radiant heat. These results were compared with intraperitoneally injected controls. We also evaluated the ability of naloxone to reverse the observed effects.

RESULTS: Intradermal injection of each NSAID produced a dose-dependent increase in tail-flick latency. Intraperitoneal NSAIDs injection produced no antinociceptive effects. Naloxone pretreatment had no effect on the antinociceptive effects of intradermal diclofenac, ketorolac, lysine acetyl salicylate, and sodium salicylate. Naloxone completely blocked the antinociceptive effects of intradermal dipyrone.

CONCLUSIONS: Local, but not systemic, administration of NSAIDs produced antinociception in the tail-flick thermal assay. The endogenous opioid system contributes to the peripheral antinociceptive effects of dipyrone, but not to that of diclofenac, ketorolac, lysine asetyl salicylate, or sodium salicylate, suggesting differences in the mechanisms of action among the NSAIDs.

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