Effect of melatonin on peripheral neuropathic pain in diabetic rat

ABSTRACT

Diabetes mellitus is often accompanied by chronic neuropathic pain. Studies indicate that oxidative stress has an important role in the appearance of neurological and behavioral changes in diabetes. Necessitating researching therefore the antioxidants effects in alleviation of diabetic neuropathic pain. In this study, 32 male Wistar rats weighing 200 +/- 20 g were used, and were divided into four groups Control[C], melatonin[M], diabetic[D] and melatonin-treated diabetic[MD]. Experimental diabetes was induced by intraperitoneal injection of 50 mg/kg streptozotocin [STZ]. Melatonin was injected [10 mg/kg/day, i.p.] for 2 weeks, after 21 days of diabetes induction. At the end of administration period, nociceptive biphasic behavior in rats was assessed using the 0.5% formalin test, and then observed for up to 60 min, according to spontaneous flinching and licking responses. In this study, lipid peroxidation levels, glutathione-peroxidase and catalase activities were measured in spinal L4-S3 dorsal root ganglia. Experimental data were then statistically analyzed Formalin-evoked flinching increased in both acute and chronic phases of pain in diabetic rats as compared to non-diabetic ones, whereas administration of melatonin reduced flinching frequency in both phases in MD rats. Total time of licking in diabetic rats was significantly [p < 0.05] more than the control rats in both acute and chronic phases of pain melatonins injection significantly reduced this time in both phases of pain in the MD as compared D group, whereas was no significant difference between M and C rats in the indices mentioned. Assessment of dorsal root ganglia homogenates indicated an increase in Lipid peroxidation levels and a decrease in GSH-Px and CAT activities in the D group as compared to the controls [C]. While melatonin administration ameliorated these in diabetic rats. Results suggest that oxidative stress contributes to appearance of pain in diabetes and melatonin, as an antioxidant, is effective in reducing the acute and chronic pain in diabetic rats