ISOBOLOGRAPHIC ANALYSIS OF INTERACTIONS BETWEEN INTRAVENOUS MORPHINE,PROPACETAMOL AND DICLOFENAC IN CARRAGEENAN-INJECTED RATS

Background: It has been suggested that the combination of analgesic dr ugs may have additive or synergistic effects. In clinical practice, th is might allow better analgesia and reduction of side effects, Methods : The effects of analgesic drugs were studied in a model of acute infl ammatory pain in carrageenin-injected rats using the vocalization thre shold to paw pressure. A combination of three different intravenous dr ugs were used: morphine, diclofenac, and propacetamol, a pro-drug of a cetaminophen, The dose-response curves were first obtained for each dr ug 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 thereaf ter evaluated and compared with the effects of the drugs alone. Result s: For the two different ratios tested, synergy between diclofenac and morphine was observed only with the higher doses. Propacetamol and mo rphine or diclofenac and propacetamol combinations were additive for a ll doses tested, Conclusions: This study found a synergy between intra venous morphine and diclofenac that is consistent with and helps expla in the clinical value of this type of combination in the treatment of acute pain in humans.