Combining an NSAID and paracetamol (acetaminophen) has in some studies given superior analgesia compared with the single drugs. In other trials no additive effect has been found. We have investigated the effect of this drug combination on the pressure pain tolerance threshold (PPTT), a reproducible correlate to clinical pain. The aim of this double blind, randomised, placebo controlled, crossover study was to evaluate the effect of i.v. propacetamol 2 g (= paracetamol 1 g) and ketorolac 30 mg, individually and in combination, on PPTT in 16 volunteers on four separate days. PPTT was measured 15 min before and at 45, 60, 90 and 150 min after the start of test drug administration. The pressure stimuli were applied on the base of a fingernail, increasing by 30 kPa/s until the pressure pain tolerance threshold was reached. For the total observation period (150 min), only the combination (propacetamol+ketorolac) increased significantly PPTT compared with baseline (P<0.04), while PPTT decreased significantly after placebo (P<0.01). The combination (propacetamol+ketorolac) and ketorolac alone increased PPTT compared with placebo (combination vs. placebo and ketorolac vs. placebo, P<0.001) and with propacetamol (combination vs. propacetamol and ketorolac vs. propacetamol, P<0.001). The combination was significantly better than ketorolac alone (P<0.04). After propacetamol 2 g, PPTT did not change significantly neither compared with placebo or baseline.
Conclusions: Tolerance to repeated painful pressure (PPTT) decreased after placebo. Ketorolac 30 mg caused an increase in PPTT compared with placebo but not with baseline. Adding propacetamol 2 g to ketorolac 30 mg significantly increased PPTT. These findings support the practice of combining paracetamol with an NSAID for relief of acute pain.