Ameliorative potential of flavonoids of Aegle marmelos in vincristine-induced neuropathic pain and associated excitotoxicity.

Introduction: The objective of the study is to elucidate the effect of Aegle marmelos bark hydroalcoholic extract (AMHE) and the role of its constituents marmelosin, umbelliferone, and Para-coumaric acid in attenuating neuropathic pain. Methodology: Peripheral neuropathy was induced by vincristine 100 μg/ml. AMHE was administered in three dose levels (100, 200 and 300 mg/kg) for 21 days. Mechanical hyperalgesia and allodynia were assessed by Randall Sellitto and electronic Von-Frey test, respectively. Functional loss and recovery of the nerve were assessed by sciatic functional index test. The nerve conduction velocity and formalin test were done to assess the peripheral and central response of the extract. Inflammatory mediators in both sciatic nerve and brain and neurotransmitters glutamate and aspartate were measured to support the data. Results and discussion: The inflammatory mediators in both sciatic nerve and brain (TNF-α, IL-1β, and IL-6) were found to be attenuated with AMHE-treated group in comparison to the group treated only with vincristine, which indicates the extract has anti-inflammatory property. AMHE treated rats were found to be active in all the behavioural tests, suggesting its activity could be mediated through a central and peripheral mechanism to attenuate the pain response. The levels of excitatory neurotransmitters were found to be reduced with AMHE treatment. Conclusion: It could be concluded that AMHE is active in attenuating the neuropathic pain caused by vincristine. The peripheral action would have mediated through lowering the inflammatory mediators as well as the excitotoxicity caused due to peripheral neuropathy and neuroinflammation.