Analgesic effects of naringenin in rats with spinal nerve ligation-induced neuropathic pain

Naringenin, a flavonoid abundant in citrus fruits, such as grapefruits, has been reported to possess antiinflam-matory properties. The present study aimed to investigate the analgesic potential of naringenin in L5 spinal nerve ligation (SNL)-induced peripheral neuropathic pain and the underlying mechanisms associated with neuroinflammation. Different doses of naringenin or saline were administered intrathecally once daily for 11 consecutive days, from 3 days prior to surgery to 7 days after surgery. Pain development was assessed 1 day prior to and 7-14 days after surgery in terms of mechanical withdrawal threshold and thermal withdrawal latency. Astrocytic and microglial activation and production of inflammatory mediators were determined on day 14 after surgery. The results demonstrated that naringenin dose-dependently attenuated the mechanical allodynia and thermal hyperalgesia induced by SNL. Furthermore, naringenin significantly inhibited SNL-induced activation of glial cells (astrocytes and microglia). Morover, the upregulated expression of inflammatory mediators in neuropathic pain was significantly inhibited by naringenin. Our findings suggested that repeated administration of naringenin may alleviate neuropathic pain, possibly through inhibiting neuroinflammation.