The local antinociceptive actions of nonsteroidal antiinflammatory drugs in the mouse radiant heat tail-flick test.
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 mug 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 acetyl salicylate, or sodium salicylate, suggesting differences in the mechanisms of action among the NSAIDs.
Dogrul
Ahmet
A
Department of Pharmacology, Gülhane Academy of Medicine, Etlik, Ankara, Turkey.
Gülmez
S Ezgi
SE
Deveci
M Salih
MS
Gul
Husamettin
H
Ossipov
Michael H
MH
Porreca
Frank
F
Tulunay
F Cankat
FC
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006358:Hot Temperature; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D020910:Ketorolac / Q000494:pharmacology; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D011930:Reaction Time / Q000187:drug effects; D012980:Sodium Salicylate / Q000494:pharmacology; D013623:Tail / Q000294:innervation; D013997:Time Factors
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009292:Narcotic Antagonists; D004008:Diclofenac; D009270:Naloxone; D004177:Dipyrone; D008239:Lysine; D001241:Aspirin; D012980:Sodium Salicylate; C010395:acetylsalicylic acid lysinate; D020910:Ketorolac