Farnesol, a sesquiterpene alcohol, has been shown to have antioxidant and anti-inflammatory properties. Recent studies have found that antioxidant compounds may exert a certain protective effect against neurotoxicity. The objective of this study was to evaluate the antinociceptive activity of farnesol (FAR) and its neurotoxic effects on the brains of adult mice. In this study, two mouse models of analgesia were used to evaluate FAR at doses of 50, 100, and 200 mg/kg, injected intraperitoneally (i.p.). In the acetic acid-induced writhing test, a significant decrease was found in the number of contortions in the FAR-treated mice at doses of 50, 100, and 200 mg/kg. FAR was also found to inhibit the licking response in the injected paw at doses of 100 and 200 mg/kg (i.p.) in the first (0-5 min) and second phases (15-30 min) of the formalin test. To evaluate neurotoxic effects, Swiss mice were treated with 0.9% saline (i.p., control group), 0.05 Tween 80 dissolved in 0.9% saline (i.p., vehicle group), and FAR 50, 100, or 200 mg/kg, i.p. Following treatment, all groups were observed for 72 h. In the FAR 200-mg group, 16% of the animals suffered brain injury that affected 12% of the area of the hippocampus. No lesions were found in the hippocampal and striatal regions of the brain in any of the animals treated with the 50 and 100 mg/kg doses of FAR. In conclusion, FAR exerts an antinociceptive effect with no significant neurotoxicity in the brains of adult mice.

Perillyl alcohol (PA) is a natural compound found in essential oils. In this study, the antinociceptive activity of PA was evaluated using acetic acid and formalin tests. The involvement of the opioid system in its mechanism of action was investigated. Potential histological changes in the hippocampus and striatum were also assessed. In the acetic acid induced writhing tests, the mice pretreated with PA exhibited significant reductions in writhing. PA inhibited formalin injected paw licking response, and naloxone partially reversed the antinociceptive activity of perillyl alcohol during the writhing test. And as for the histopathological evaluation, PA did not cause significant tissue changes. This study suggests that PA possesses antinociceptive effects without significant hippocampus or striatum neurotoxicity, and that its activity involves opioid.