Evaluation of the preventive effects of Achillea millefolium and Sodium valproate on neuropathic pain caused by Cisplatin in mice

Abstract

Introduction: One of the side effects of cisplatin is peripheral neuropathy. There are various mechanisms in peripheral neuropathy caused by this drug, including increased function of the glutaminergic system and induction of oxidative stress. Sodium valproate and Achillea millefolium have different pharmacological effects and have antioxidant effects. Aim: In this thesis, the prophylactic effect of sodium valproate and Achillea millefolium extract on cisplatin-induced neuropathic pain in male mice was investigated. Material and Methods: In this study, 80 male mice were randomly divided into 10 groups of 8. They received regimens include normal saline, sodium valproate in different doses (25,50,100 mg/kg), Achillea millefolium hydroalcoholic extract in different doses (50,100,200 mg/kg), combined dose (25 mg/kg valproate + 50 mg/kg extract) and DMSO solvent with a concentration of 25%. Cisplatin was injected into the animals as a neuropathic inducer. Hot plate test was performed to evaluate the animal's sensitivity to pain. Finally, blood samples were taken from animals to assay MDA and TAC. Results: Different doses of sodium valproate and Achillea millefolium extract significantly increased Hot Plate test results and decreased pain sensitivity. In addition, 100 mg/kg valproate was able to significantly reduce the MDA biomarker. Co-administration of sodium valproate and Achillea millefolium extract did not show any statistically significant change in Hot plate results. Conclusion: Sodium valproate may reduce the symptoms of neuropathy and increase pain tolerance in the studied groups by reducing glutamate-induced stimulation in NMDA receptors and inhibiting serotonin transport. Sodium valproate may also reduce the symptoms of cisplatin-induced neuropathy by increasing repolarization and decreasing the action potential on neuronal membranes. Achillea millefolium extract probably reduces neuropathic pain caused by cisplatin by inhibiting oxidative stress due to its antioxidant flavonoids.