CHARACTERIZATION OF THE ANALGESIC EFFECTS OF PARACETAMOL AND CAFFEINECOMBINATIONS IN THE PAIN-INDUCED FUNCTIONAL IMPAIRMENT MODEL IN THE RAT

The analgesic activities of paracetamol (100, 178, 316 and 562 mg kg-1 ), caffeine (10, 18, 32 and 56 mg kg-1) and combinations of these dose s were tested on a pain-induced functional impairment model in the rat . Dysfunction of the right hind limb was induced by an intra-articular injection of 30% uric acid in the knee. Drugs were given orally and t he recovery of functionality over time was considered as an expression of analgesia. Paracetamol alone induced a dose-dependent analgesic ef fect whereas caffeine alone did not show any activity at the assayed d oses. Combinations of 316 mg kg-1 paracetamol with either 10, 18, 32 o r 56 mg kg-1 caffeine yielded analgesic effects significantly greater than that of paracetamol alone. The highest potentiation was observed with a paracetamol-caffeine mixture of 316-32 mg kg-1. Caffeine coadmi nistration, however, did not significantly change paracetamol plasma l evels. No potentiation was obtained with other combinations. Paracetam ol plasma levels and analgesic effect observed with administration of 316 mg kg-1 paracetamol alone or 316-32 mg kg-1 of paracetamol-caffein e were fitted to the sigmoidal E(max) model according to the Hill equa tion. The curves obtained were parallel, but that of the combination w as shifted to the left. It is concluded that caffeine is able to poten tiate the analgesic effect of paracetamol by a pharmacodynamic mechani sm, but this only occurs at certain dose combinations.