Comparison of antinociceptive efficacy and gastroprotection between celecoxib and diclofenac plus misoprostol in rats

The present study was designed to assess the antinociceptive efficacy and gastroprotective activity of the mixture of diclofenac and misoprostol and its comparison with celecoxib in rats. The effect of diclofenac/misoprostol and celecoxib was assessed in the 1% formalin test. Female Wistar rats were fasted 12 hr before experiments and diclofenac (10 and 50 mg/kg), misoprostol (100 μg/kg), celecoxib (30 and 100 mg/kg), saline and the combination of diclofenac (50 mg/kg) plus misoprostol (25, 50 and 100 μg/kg) were administered orally. Nociceptive behavior was assessed during the following hr. Diclofenac and celecoxib dose-dependently reduced formalin-induced nociception reaching similar maximal effects. Moreover, misoprostol did not produce antinociception, but increased diclofenac-induced antinociception. Animals were sacrificed 3 hr following drug administration and stomachs examined to assess gastric damage. Misoprostol did not produce any damage to the stomach. However, diclofenac, but not celecoxib, produced significant gastric damage (number of stomach ulcers) in a dose-dependent fashion. Misoprostol dose-dependently reduced diclofenac-induced ulcers. Data show that diclofenac and celecoxib lead to similar antinociception, with diclofenac being more active to produce gastric damage. However, diclofenac-induced gastric damage can be markedly reduced by misoprostol. In addition to its gastroprotective effect, misoprostol showed a synergic effect on diclofenac-induced anti-nociception. Considering the cardiovascular effects of COX-2 selective inhibitors, the combination of diclofenac and misoprostol could represent a safer and effective alternative for patients with pain.