Involvement of the NO/cGMP/KATP pathway in the antinociceptive effect of rosemary (Rosmarinus officinalis) essential oil in mice

Abstract

Rosemary essential oil (REO) has been used for several medical purposes. Previous studies have shown the antinociceptive effect of the oil. This study aimed to investigate the role of some well-known receptors in the antinociceptive effect of REO. Male Swiss mice (25–30 g) were used. To assess the antinociceptive activity, the formalin test was used. At first, the antinociceptive effect of three doses of rosemary oil (150, 300 and 450 µL/kg) was tested, and then a dose of 300 µL/kg was selected for the mechanistic study. Animals were pretreated with several antagonists and enzyme inhibitors to evaluate the role of adrenergic, cholinergic, serotoninergic, dopaminergic and opioid receptors as well as the NO/cGMP/KATP pathway in the antinociceptive effect of rosemary essential oil. Yohimbine (5 mg/kg), prazocin (2 mg/kg), propranolol (2 mg/kg), atropine (2.5 mg/kg) naloxone (5 mg/kg), cyproheptadine (2 mg/kg), ondansetron (2 mg/kg) and haloperidol (1 mg/kg) could not reverse the antinociceptive effect. Sulpiride (20 mg/kg) only showed preventive activity in the early phase of formalin test while methylene blue (5 mg/kg), L-NAME (20 mg/kg) and glibenclamide (10 mg/kg) significantly attenuated the antinociceptive effect of REO in both phases. Tadalafil (2 mg/kg) potentiated the antinociceptive effect of REO in the late phase of formalin test and arginine (100 mg/kg) had no effect on both phases. Therefore the NO/cGMP/KATP pathway might have an important role in the antinociceptive effect of REO.

Anti-inflammatory and antinociceptive effects of sitagliptin in animal models and possible mechanisms involved in the antinociceptive activity

“…All drugs were injected intraperitoneal except formalin that was injected subcutaneously (s.c.). The doses were selected based on previous studies [ 14 , 15 ]. In another series of animals, the same doses of the above-mentioned drugs were used without sitagliptin.…”