Protective effect of hesperetin in rat model of partial sciatic nerve ligation induced painful neuropathic pain: an evidence of anti-inflammatory and anti-oxidative activity.

Behavioral, biochemical and gene expression changes were investigated in a rat model of partial sciatic nerve ligation (PSNL) after administration of hesperetin (20, 50mg/kg; p.o.), pregabalin (10mg/kg; p.o.) or vehicle (1 ml/kg, p.o.). Thirty-six animals were randomly divided into six groups. Left sciatic nerve was exposed and ligated, animals in the control and test groups were treated orally with respective drugs for fifteen days. Nociceptive threshold was assessed on 0 day and thereafter every three days. Three weeks later, sciatic nerve tissue homogenate was prepared and subjected for estimation of oxidative markers namely total protein, nitric oxide, lipid peroxidase, interleukins (IL-1β and IL-6) and TNF-α. Administration of hesperetin resulted in a dose dependent attenuation in PSNL-induced mechanical and thermal hyperalgesia, mechanical allodynia as well as down regulation of IL-1β, IL-6 and TNF-α, and biochemical markers. Consequently, it can be concluded that anti-hyperalgesic effect of hesperetin in rats after PSNL may be attributed to various oxidative markers as well as the pro-inflammatory mediators secreted at the injury site. Hesperetin appears to be a promising candidate for the development as a novel therapeutic for the patients suffering from the neuropathic pain.