Shahrekord University of Medical Sciences Journal of Shahrekord University of Medical Sciences 2717-0071 28 1 2026 04 20 Opposing Effect Against Oxidative Stress Imbalance in the Prefrontal Cortex Partly Mediates Analgesic Properties of Anethole in Maternally Separated Female Mice 23 28 10.34172/jsums.1087 EN Shima Balali-Dehkordi https://orcid.org/0000-0003-3884-4973 Ramina Khodadadian https://orcid.org/0009-0006-8974-3987 Behnaz Karimi Babaahmadi https://orcid.org/0000-0003-1922-4656 Mohammad Shadkhast https://orcid.org/0000-0002-5066-7263 Journal Article 10.34172/jsums.1087 2025 08 03 2025 09 13 Background and aims: Oxidative stress (OS) is involved in the physiopathology of pain response, and maternal separation (MS) stress is accompanied by OS imbalance in the brain. Anethole is a natural compound with neuroprotective effects. Accordingly, this trial study aimed to estimate the analgesic effect of anethole in female mice undergoing MS stress, with a focus on OS imbalance in the prefrontal cortex (PFC). Methods: In general, 28 female mice were used in this experimental study. MS mice received saline (10 mL/kg) or anethole (62.5 mg/kg and 125 mg/kg), while control mice received saline (10 mL/kg). One hour after treatment, the animals underwent pain assessment tests, including the tail flick and hot plate tests. Moreover, malondialdehyde (MDA) and total antioxidant capacity (TAC) were assessed in the PFC. Finally, one-way ANOVA followed by Tukey’s post hoc test was employed for statistical analysis. Results: MS in female mice was linked with a decrease in latencies in the tail flick (P=0.0133) and hot plate (P=0.014) tests, a rise in MDA (P=0.0001), and a reduction in the TAC (P=0.0001) in the PFC. Anethole increased the latencies in the tail flick (P=0.0001 for both doses) and hot plate (P=0.002 and P=0.0002 for 62.5 mg/kg and 125 mg/kg, respectively) tests. However, anethole decreased MDA (P=0.0017 for a dose of 125 mg/kg) while increasing TAC (P=0.0018 for a dose of 125 mg/kg) in the PFC. Conclusion: It was revealed that anethole, partly through OS diminution in the PFC, increased latencies to pain stimuli in MS female mice.