The local antinociceptive actions of nonsteroidal antiinflammatory drugs in the mouse radiant heat tail-flick test

Ahmet Dogrul, S. Ezgi Gülmez, M. Salih Deveci, Husamettin Gul, Michael H. Ossipov, Frank Porreca, F. Cankat Tulunay

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)927-935
Number of pages9
JournalAnesthesia and Analgesia
Volume104
Issue number4
DOIs
StatePublished - Apr 2007

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Tail
Anti-Inflammatory Agents
Hot Temperature
Dipyrone
Sodium Salicylate
Ketorolac
Pharmaceutical Preparations
Diclofenac
Naloxone
Intradermal Injections
Opioid Analgesics
Analgesics
Injections
lysine salicylate

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

The local antinociceptive actions of nonsteroidal antiinflammatory drugs in the mouse radiant heat tail-flick test. / Dogrul, Ahmet; Gülmez, S. Ezgi; Deveci, M. Salih; Gul, Husamettin; Ossipov, Michael H.; Porreca, Frank; Tulunay, F. Cankat.

In: Anesthesia and Analgesia, Vol. 104, No. 4, 04.2007, p. 927-935.

Research output: Contribution to journalArticle

Dogrul, Ahmet ; Gülmez, S. Ezgi ; Deveci, M. Salih ; Gul, Husamettin ; Ossipov, Michael H. ; Porreca, Frank ; Tulunay, F. Cankat. / The local antinociceptive actions of nonsteroidal antiinflammatory drugs in the mouse radiant heat tail-flick test. In: Anesthesia and Analgesia. 2007 ; Vol. 104, No. 4. pp. 927-935.
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AU - Ossipov, Michael H.

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N2 - 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.

AB - 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.

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