The combination of naproxen and citral reduces nociception and gastric damage in rats

Abstract

It has been shown that the association of non-steroidal anti-inflammatory drugs with plant extracts 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 interaction between naproxen and citral on nociception and gastric injury in rats. Naproxen, citral, or combinations of naproxen and citral produced an antinociceptive effect. The administration of naproxen produced significant gastric damage, but this effect was not obtained with either citral or the naproxen-citral combination. The ED(50) value was estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED(50) for the antinociceptive effect (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 antinociceptive effect is additive. These data suggest that the naproxen-citral combination interacts at the systemic level, produces minor gastric damage, and potentially has therapeutic advantages for the clinical treatment of inflammatory pain.

Supra‐Additive Interaction of Docosahexaenoic Acid and Naproxen and Gastric Safety on the Formalin Test in Rats

“…These results demonstrate that the antinociceptive efficacy of DHA, naproxen, and the DHAnaproxen combination treatment is consistent with previous reports that showed the antinociceptive effect of oral naproxen [Ortiz et al, 2010]; and oral and local DHA [Nakamoto et al, 2010;Arroyo-Lira et al, 2014;Landa-Ju arez et al, 2016]. Moreover, to the best of our knowledge, this study provides the first demonstration that systemic administration of the DHA-naproxen (1:3) combination possesses supra-additive antinociceptive effects in the formalin test.…”

“…Combinations of NSAIDs with other analgesic agents appear to be an effective strategy to reduce NSAID exposure, allowing the use of lower doses of each agent [Tallarida, 2001;Arroyo-Lira et al, 2014 ], since it has been reported that gastric toxicity is strongly influenced by the amount of NSAIDs [Seo et al, 2012]. Thus, the combination of NSAIDs with natural products like DHA is an alternative to increase the antinociceptive effects without increasing side effects [Maroon et al, 2010] including gastric injury [Ortiz et al, 2010]. In our study, we showed that oral administration of naproxen induced gastric damage.…”

Monoterpenes with Analgesic Activity—A Systematic Review

“…In animals, citral promoted a decrease of nociceptive response in several models of nociception and was able to reduce paw oedema and leukocyte migration, both induced by carrageenan (Quintans‐Júnior et al ., ). Combinations of naproxen and citral also produced an antinociceptive effect without causing significant gastric damage, presenting therapeutic advantages for the clinical treatment of inflammatory pain (Ortiz et al ., ).…”

Evidence for the Participation of ATP-sensitive Potassium Channels in the Antinociceptive Effect of Curcumin

“…Curves were made by plotting the number of flinches against time. The area under the number of flinches against time curves (AUC) was calculated by the trapezoidal rule [17,28-30]. AUC was calculated for the two phases of the assay, and the percent of antinociception for each phase was calculated according to the following equation [30]:…”