ANALGESIC EFFECTS OF COMBINATIONS CONTAINING OPIOID DRUGS WITH EITHERASPIRIN OR ACETAMINOPHEN IN THE RAT

The analgesic effects of combinations of either aspirin or acetaminoph en with morphine, d-propoxyphene, and pentazocine were studied in the pain-induced functional impairment in the rat model (PIFIR). Pain was induced by the intra-articular injection of uric acid in the right hin d limb inducing its dysfunction. Animals then received analgesic agent s, and the recovery of functionality over time was assessed as an expr ession of analgesia. The combination of aspirin with either morphine o r d-propoxyphene resulted in analgesic effects similar to those expect ed on the basis of addition of the effects of the individual component drugs. However, the combination of aspirin and pentazocine resulted i n a potentiation (46%), the observed analgesia being significantly gre ater than the expected effect. Coadministration of acetaminophen and m orphine resulted in an analgesic effect that was not different from th at expected on the basis of addition, whereas acetaminophen with d-pro poxyphene resulted in a lower effect (21%). Moreover, the combination of acetaminophen and pentazocine resulted in an effect that was simila r to that seen with either acetaminophen or pentazocine alone. The per cent change in combination was 41% lower than the addition of the indi vidual effects. It appears that, while certain combinations of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) may be beneficial, other combinations may be detrimental. Therefore, great care should be taken in the choice of the components of analgesic drug mixtures. Pre clinical pharmacological information about the efficacy of drug associ ations should be taken into consideration before testing in humans. (C ) 1993 Wiley-Liss, Inc.