Isobolographic Analysis of Interactions between Intravenous Morphine, Propacetamol, and Diclofenac in Carrageenin-injected Rats

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Abstract
Background: It has been suggested that the combination of analgesic drugs may have additive or synergistic effects. In clinical practice, this might allow better analgesia and reduction of side effects. Methods: The effects of analgesic drugs were studied in a model of acute inflammatory pain in carrageenin-injected rats using the vocalization threshold to paw pressure. A combination of three different intravenous drugs were used: morphine, diclofenac, and propacetamol, a pro-drug of acetaminophen. The dose-response curves were first obtained for each drug alone. The analgesic potencies of the combinations of morphine and diclofenac (ratios, 1:5.66 and 1:10), morphine and propacetamol (ratio, 1:250), and diclofenac and propacetamol (ratio, 1:65.7) were thereafter evaluated and compared with the effects of the drugs alone. Results: For the two different ratios tested, synergy between diclofenac and morphine was observed only with the higher doses. Propacetamol and morphine or diclofenac and propacetamol combinations were additive for all doses tested. Conclusions: This study found a synergy between intravenous morphine and diclofenac that is consistent with and helps explain the clinical value of this type of combination in the treatment of acute pain in humans.