Effect of Topiramate on Mitochondrial Biogenesis and Neuroinflammation in Chronic Constriction Injury and Streptozotocin-induced Peripheral Neuropathy

Abstract:

Background: Because neuropathic pain is currently a poorly understood medical condition, there is a need to identify a more effective therapeutic drug with a low toxicity profile. Purpose: To address the behavioural, oxidative stress, and cytokine-mediated inflammatory pathways involved in sciatic nerve, the current study protocol used Chronic Constriction Injury (CCI) and Streptozotocin (STZ) induced neuropathic pain methods. Materials and Methods: Following CCI to the sciatic nerve and administration of STZ 60mg/kg, rats develop painful neuropathy characterized by hyperalgesia, allodynia, oxidative stress, neuroinflammation, and increased total calcium levels. Results: Topiramate (20, 40, and 80 mg/kg) treatment for two weeks beginning on the 15th day of CCI surgery and ending on the 29th day of diabetes confirmation significantly and dose dependently reduced the development of allodynia and hyperalgesia. Furthermore, topiramate treatment produced significant dose-dependent antioxidant and anti-inflammatory effects by restoring the balance of oxidative stress and decreasing the levels of inflammatory markers such as TNF-a, IL-1, and IL-6, as well as total calcium in sciatic nerve homogenate. Conclusion: To summarize, the treatment with different doses of topiramate produces analgesic, antioxidant, and anti-inflammatory effects in a dose dependent manner, owing to the increased curiosity to understand the underlying pain producing mechanism and its translation into signs and symptoms of CCI and STZ induced neuropathy.

Keywords: Topiramate, CCI, STZ, Oxidative Stress, Cytokines.