Synergy between the antinociceptive effects of morphine and NSAIDs

H. F. Miranda, E. Silva, G. Pinardi

Research output: Contribution to journalArticle

36 Citations (Scopus)


The intraperitoneal administration of morphine, diclofenac, ketoprofen, meloxicam, metamizol, paracetamol and piroxicam induced dose-dependent antinociception in mice tested with the acetic acid writhing test. The isobolographic analysis of the simultaneous intraperitoneal administration of fractions of the ED50's of morphine with each nonsteroidal anti-inflammatory drug (NSAID) demonstrated the existence of a supra-additive interaction (synergy). The selective antagonist of μ-opioid receptors naltrexone partially reversed the supra-additive interactions to additive interactions; however, the combinations of morphine/metamizol and morphine/paracetamol were completely antagonized, resulting in subadditive interactions. The selective antagonist of δ-opioid receptors naltrindole failed to significantly attenuate the combinations of morphine with ketoprofen, meloxicam and piroxicam, but decreased the activity of the combinations of morphine with diclofenac, metamizol and paracetamol, transforming the interactions from supra-additive to additive. Nor-binaltorphimine was used to evaluate the involvement of κ-opioid receptors. Nor-binaltorphimine did not modify the supra-additive interaction of morphine and NSAIDs and the additive interaction of the co-administration of morphine and metamizol. The synergy between morphine and NSAIDs could be related to different pathways of pain transmission, probably related to the different intracellular signal transduction mechanisms of action of opioid and non-opioid agents.

Original languageEnglish
Pages (from-to)331-338
Number of pages8
JournalCanadian Journal of Physiology and Pharmacology
Issue number5
Publication statusPublished - May 2004


  • Antinociception
  • Isobolographic analysis
  • Morphine
  • NSAIDs
  • Synergy
  • Writhing test

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Synergy between the antinociceptive effects of morphine and NSAIDs'. Together they form a unique fingerprint.

  • Cite this