7-Hydroxyflavone mitigates partial sciatic nerve ligation-induced neuropathic pain via modulation of oxidative and inflammatory pathways.

Chronic neuropathic pain is a common and widely recognized pain syndrome that remains difficult to manage clinically. Although several therapeutic options exist, many are limited by inadequate efficacy and adverse effects which underscore the need for safer and more effective alternatives. 7-Hydroxyflavone (7-HF), a natural occurring flavonoid, has demonstrated diverse biological properties, and limited evidence suggests its antinociceptive potential in chemotherapy-induced neuropathic pain. However, its therapeutic effects and mechanistic involvement in partial sciatic nerve ligation (PSNL)-induced neuropathic pain model remain insufficiently explored. The present study aimed to investigate the therapeutic role of 7-HF in PSNL-induced neuropathic pain in rats. Neuropathic pain was induced in Wistar rats by the PSNL procedure. Following surgery, rats were treated with 7-HF (5 and 10 mg/kg) and pregabalin (20 mg/kg) for 22 consecutive days. PSNL produced significant thermal hypersensitivity (reduced withdrawal latency), along with decreased pain response latency, reduced fall-off time (duration rats remained on the rotarod apparatus before falling), and diminished locomotor activity. These behavioral alterations were accompanied by enhanced oxidative stress (elevated LPO with reduced GSH and SOD) and increased inflammatory cytokines (TNF-α and IL-6). Treatment with 7-HF significantly attenuated these behavioral and biochemical changes, reduced oxidative and inflammatory markers, and improved sciatic nerve histopathology, with greater protective effects observed at the higher tested dose. These findings suggest that 7-HF alleviates PSNL-associated nociceptive and neuroinflammatory alterations, likely through antioxidant and anti-inflammatory actions. This study extends existing evidence and supports 7-HF as a promising candidate for further investigation in neuropathic pain management.