Background and Purpose <p>Neuropathic pain is a chronic and disabling condition characterized by persistent sensory hypersensitivity and inadequate treatment options. Neuroinflammation and TRPV1/CGRP-driven nociceptive pathways are critical contributors to its pathogenesis. Bergenin, a naturally occurring C-glucoside with established anti-inflammatory and antioxidant activities, may offer a promising therapeutic approach.</p> Experimental Approach <p> Neuropathic pain was induced in rats using the chronic constriction injury (CCI) model. Bergenin (25, 50, and 100 mg/kg, i.p.) and gabapentin (30 mg/kg, i.p.) were administered. Nociceptive behaviors were evaluated using von Frey, paintbrush, pinprick, Hargreaves, acetone spray, and ice floor tests. Locomotor activity and motor coordination were assessed to examine CNS safety. Oxidative stress parameters and the expression of TNF-α, IBA1, ICAM1, TRPV1, and CGRP were measured in spinal cord tissue.</p> Key Results <p> CCI produced marked mechanical, thermal, and cold hypersensitivity, accompanied by elevated oxidative stress and increased neuroinflammatory marker expression. Bergenin significantly attenuated pain-related behaviors across all tested doses, with enhanced efficacy at higher doses, and improved oxido-nitrosative status. Furthermore, it downregulated TNF-α, IBA1, ICAM1, TRPV1, and CGRP expression while producing no detectable impairment in locomotor activity or motor coordination.</p> Conclusion and Implications <p>Bergenin alleviates neuropathic pain by modulating neuroinflammatory pathways and TRPV1/CGRP signaling while reducing oxido-nitrosative stress, without affecting locomotor activity or motor coordination. These findings support its potential as a non-opioid therapeutic strategy for the management of neuropathic pain</p>