The Combination of Naproxen and Citral Reduces Nociception and Gastric Damage in Rats

It has been shown that the association of non-steroidal anti-inflammatory drugs with plantextracts can increase their antinociceptive activity, allowing the use of lower doses and, thus,limiting side effects. Therefore, the aim of this study was to examine the effects of the interactionbetween naproxen and citral on nociception and gastric injury in rats. Naproxen, citral,or combinations of naproxen and citral produced an antinociceptive effect. The administrationof naproxen produced significant gastric damage, but this effect was not obtained with eithercitral or the naproxen-citral combination. The ED50 value was estimated for the individualdrugs and an isobologram was constructed. The derived theoretical ED50 for the antinociceptiveeffect (423.8 mg/kg) was not significantly different from the observed experimental value(359.0 mg/kg); hence, the interaction between naproxen and citral mediating the antinociceptiveeffect is additive. These data suggest that the naproxen-citral combination interacts atthe systemic level, produces minor gastric damage, and potentially has therapeutic advantagesfor the clinical treatment of inflammatory pain.