Prophylactic Effect of Echinacoside on PIPN by Inhibiting Spinal Neuroinflammation and Exerting Neuroprotective...

Paclitaxel leads to peripheral neuropathy (PIPN) in approximately 50 % of cancer patients. At present, there are no effective treatment strategies, and the mechanisms of which also remain unclear. Echinacoside (ECH), a natural compound with known neuroprotective, antioxidant and anti-inflammatory properties, holds significant therapeutic potential for PIPN. However, the precise mechanism of its action remains unknown. In this study, we aimed to investigate the effectiveness of echinacoside in a mouse model of neuropathic pain induced by paclitaxel, as well as the underlying mechanisms. Administration of paclitaxel (2.0 mg/kg on four alternate days) induced acute mechanical /cold/thermal hypersensitivity in mice. Treatment with echinacoside significantly alleviated pain behavior. Furthermore, paclitaxel led to microglia and astrocyte activation and upregulation of inflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6 in the spinal cord. These neuroinflammatory responses were reversed by echinacoside treatment. Additionally, echinacoside can attenuate the loss of hind paw nerve fibers induced by paclitaxel administration. Our findings demonstrate that echinacoside reduces paclitaxel-induced neuropathic pain by attenuating microglia and astrocyte reactivity, neuroinflammatory processes in spinal cord and alleviating the loss of peripheral nerve fibers.