Isobolographic analysis of the opioid-opioid interactions in a tonic and a phasic mouse model of induced nociceptive pain

Hugo F. Miranda, Viviana Noriega, Pilar Zanetta, Juan Carlos Prieto, Juan Carlos Prieto-Rayo, Nicolás Aranda, Fernando Sierralta

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Background: Opioids have been used for the management of pain and coadministration of two opioids may induce synergism. In a model of tonic pain, the acetic acid writhing test and in a phasic model, the hot plate, the antinociceptive interaction between fentanyl, methadone, morphine, and tramadol was evaluated. Results: The potency of opioids in the writhing test compared to the hot plate assay was from 2.5 (fentanyl) to 15.5 (morphine) times, respectively. The ED50was used in a fixed ratio for each of the six pairs of opioid combinations, which, resulted in a synergistic antinociception except for methadone/tramadol and fentanyl/tramadol which were additive, in the hot plate. The opioid antagonists naltrexone, naltrindole and nor-binaltorphimine, suggests that the synergism of morphine combinations are due to the activation of MOR subtypes with partially contribution of DOR and KOR, however fentanyl and methadone combinations are partially due to the activation of MOR and DOR subtypes and KOR lack of participation. The antinociceptive effects of tramadol combinations, are partially due to the activation of MOR, DOR and KOR opioid subtypes. Conclusion: These results suggets that effectiveness and magnitude of the interactions between opioids are dependent on pain stimulus intensity.

Original languageEnglish
Article number62
JournalJournal of Biomedical Science
Issue number1
Publication statusPublished - 15 Jul 2014


  • Acetic acid writhing test
  • Hot plate assay
  • Interaction opioid-opioid
  • Isobolographic analysis
  • Synergism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)


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