فهرست نشریات علمی دسترسی آزاد ایران

Background: Sex differences can influence the effects of opioid and non-opioid analgesics. This study evaluated the antinociceptive effects of L-menthol in male and female mice.Methods: This experimental study was conducted in 2024 at Shiraz University of Medical Sciences (Shiraz, Iran). Forty-two BALB/c mice (21 males, 21 females) were randomLy allocated into three groups of seven mice receiving intraperitoneal injection of vehicle 2 mL/Kg, L-menthol 2.5 mg/Kg, and L-menthol 5 mg/Kg. Chemical and thermal nociception were assessed using the acetic acid-induced writhing and the hot plate tests (55 ℃, with a cut-off point of 30 seconds). The number of abdominal writhing counted for 20 min, and the percent of maximum possible effect (%MPE) calculated from the hot plate test response were used as acute pain indexes, respectively. Possible side effects and motor coordination were assessed using video behavior recording and the rotarod test, respectively. Data were analyzed by ANOVA, Tukey’s post hoc test, McNamar’s, and Kruskal-Wallis tests. Statistical significance was defined as P<0.05. Results: L-menthol 2.5 (P<0.001) and 5 mg/Kg (P<0.001) showed significant antinociceptive effects in both male and female mice in the acetic acid and hot plate tests compared to the control groups. L-menthol 5 mg/Kg in the hot plate (P=0.027) and L-menthol 2.5 and 5 mg/Kg in the acetic acid (P<0.001) tests produced higher antinociceptive effects in males than in females. No significant differences were observed in the rotarod performance and other behavioral tests across groups.Conclusion: L-menthol produced sex dependent antinociceptive effects in mice, highlighting the importance of considering biological sex in clinical pain research.