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Updated: Aug 17, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Spinal synergy between nonselective cyclooxygenase inhibitors and morphine antinociception in mice
Hugo F Miranda1, Juan Carlos Prieto, Gianni Pinardi
1Phramacology Program, ICBM, Faculty of Medicine, University of Chile, PO Box 70.000, Santiago 7, Chile. hmiranda@med.uchile.cl
Abstract:
The antinociception induced by the intrathecal coadministration of combinations of morphine with the nonsteroidal anti-inflammatory drugs (NSAIDs) naproxen, piroxicam, metamizol, diclofenac and ketoprofen was studied by isobolographic analysis in the acetic acid writhing test of mice. The effective dose that produced 50% antinociception (ED(50)) was calculated from the log dose-response curve of intrathecally administered fixed ratio combinations of morphine with each NSAID. By isobolographic analysis, this ED(50) was compared to the theoretical additive ED(50) calculated from the ED(50) of morphine and of each NSAID alone. As shown by isobolograms, all the combinations were synergistic, the experimental ED(50)'s being significantly smaller than the theoretically calculated ED(50)'s. The results of this study demonstrate potent interactions between morphine and NSAIDs and validate the clinical use of the combinations of opioids and NSAIDs in pain treatment, even by the intrathecal route.
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