Orofacial antinociceptive activity of (S)-(−)-perillyl alcohol in mice: a randomized, controlled and triple-blind study

This study investigated the antinociceptive effects of (S)-(−)-perillyl alcohol (PA) on orofacial nociception in Swiss male mice using formalin-, capsaicin-, and glutamate-induced pain tests. For each test, eight animals per group were pre-treated intraperitoneally by a blinded investigator with PA (50 or 75 mg/kg), morphine, or vehicle (saline + 0.2% Tween 80). The treatment was performed before the induction of orofacial nociception by injecting formalin, capsaicin, or glutamate solution into the right area of the upper lip. The orofacial nociceptive behaviour was timed in all tests by an investigator who was blinded to the treatments. The statistical analysis was performed using confidence intervals (CI), the effect size, and power. PA blocked the orofacial nociceptive behaviour at both doses tested (P < 0.05) similarly to morphine (P > 0.05), in all tests. The effect size was high in the phase 1 formalin test for 50 mg/kg PA (95% CI 0.48-2.31, power 84.6%) and 75 mg/kg PA (95% CI 0.82-2.76, power 96.2%), in phase 2 for 75 mg/kg PA (95% CI 0.44-2.26, power 82.3%), and in the glutamate test for 75 mg/kg PA (95% CI 1.11-3.16, power 99.2%). These findings show strong evidence for the antinociceptive properties of PA in the orofacial region.