Synergism between fentanyl and tramadol in tonic inflammatory pain: The orofacial formalin test

Hugo F. Miranda, Viviana Noriega, Ramiro J. Zepeda, Fernando Sierralta, Juan C. Prieto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Opioids have been used for long time to management of pain, the coadministration of two opioids may induce synergism. The present study was conducted to determine the antinociceptive interaction between the dual mechanism of action of tramadol compared to the main of fentanyl antinociception in the orofacial formalin which represents a model of persistent cutaneous nociception in the region innervated by the trigeminal nerve. The i.p. administration of tramadol and fentanyl induced a dose-dependent antinociception with an ED50 of 2.97±0.32 mg/kg for phase I and 1.79±0.30 mg/kg for phase II and 0.062±0.0040 mg/kg in phase I and 0.041±0.0039 mg/kg in phase II, respectively. The coadministration of fentanyl with tramadol induced synergism in both phases of the test with an interaction index of 0.343 and 0.163 for phase I and phase II, respectively. This finding could be explained by the more complex pharmacology of tramadol compared to fentanyl.

Original languageEnglish
Pages (from-to)1132-1137
Number of pages6
Issue number3
Publication statusPublished - Jun 2012


  • Isobolographic analysis, synergism, orofacial formalin test
  • Opioids
  • Tonic inflammatory pain

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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