Profound, non-opioid analgesia produced by the high-efficacy 5-HT1A agonist F 13640 in the formalin model of tonic nociceptive pain

L. Bardin, J. P. Tarayre, N. Malfetes, W. Koek, F. C. Colpaert

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations


Previously, we have reported that in rat models of chronic pain, in particular, the very-high-efficacy 5-HT1A agonist F 13640 induces unprecedented pain relief by novel neuroadaptative mechanisms that involve inverse tolerance and cooperation with nociceptive stimulation in producing analgesia. The present studies detailed the actions of F 13640 and other compounds in the formalin model of tonic nociceptive pain. Intraperitoneal injection of F 13640 (0.01-2.5 mg/kg; t -15 min) caused a dose-dependent and complete inhibition of the paw elevation and paw licking that occurred both early (0-5 min) and late (22.5-27.5 min) after the intraplantar injection of diluted formaldehyde (2.5%) in the rat. The extent to which F 13640 and other 5-HT1A receptor ligands inhibited these pain behaviors correlated (p < 0.05) with the extent to which they activated 5-HT1A receptors. Under similar conditions, some inhibitory effects were also observed with various agents that are known to produce analgesia by different peripheral and/or central mechanisms (e.g., opioids, NA/5-HT reuptake inhibitors, COX-2 inhibitors and other nonsteroidal anti-inflammatory drugs, gabapentin, and ABT-594). However, with the possible exception of morphine, the effects of all of these agents at nontoxic doses were lower than those of F 13640, in particular in inhibition of early paw elevation. The 5-HT1A antagonist WAY 100635, but not naloxone, antagonized the actions of F 13640. These results help to establish large-magnitude 5-HT1A receptor activation as a new molecular mechanism of profound, central analgesia and suggest that F 13640 may be particularly effective against pain arising from severe tonic nociceptive stimulation.

Original languageEnglish (US)
Pages (from-to)182-194
Number of pages13
Issue number4
StatePublished - 2003
Externally publishedYes


  • 5-HT receptors
  • Analgesic effect
  • Formalin test, rats
  • Pain

ASJC Scopus subject areas

  • Pharmacology


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