Analgesic effects of combinations containing opioid drugs with either aspirin or acetaminophen in the rat

The analgesic effects of combinations of either aspirin or acetaminophen 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 hind limb inducing its dysfunction. Animals then received analgesic agents, and the recovery of functionality over time was assessed as an expression of analgesia. The combination of aspirin with either morphine or d-propoxyphene resulted in analgesic effects similar to those expected on the basis of addition of the effects of the individual component drugs. However, the combination of aspirin with either morphine or d-propoxyphene resulted in analgesic effects similar to those expected on the basis of addition of the effects of the individual component drugs. However, the combination of aspirin and pentazocine resulted in a potentiation (46%), the observed analgesia being significantly greater than the expected effect. Coadministration of acetaminophen and morphine resulted in an analgesic effect that was not different from that expected on the basis of addition, whereas acetaminophen with d-propoxyphene resulted in a lower effect (21%). Moreover, the combination of acetaminophen and pentazocine resulted in a lower effect (21%). Moreover, the combination of acetaminophen and pentazocine resulted in an effect that was similar to that seen with either acetaminophen or pentazocine alone. The percent change in combination was 41% lower than the addition of the individual 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. Preclinical pharmacological information about the efficacy of drug associations should be taken into consideration before testing in humans. © 1993 Wiley-Liss, Inc.