Role of mTOR in spinal cord in development of diabetic neuropathic pain in rats

Abstract

Objective To evaluate the role of mTOR in spinal cord in the development of diabetic neuropathic pain in rats.Methods Sixty adult male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were used in the study.Forty-five rats among them were chosen randomly and diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60 mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L on day 3 after STZ injection.The left 15 rats received intraperitoneal injection of the equal volume of citric acid-sodium citrate buffer and served as normal control group (group C).Paw withdrawal threshold to von Frey filament stimulation was measured in the right hind paw before STZ injection and on 3,6,9,12,15,18,and 21 days after STZ injection.The diabetic rats with mechanical pain threshold decreasing by more than 50％ of the baseline were allocated to diabetic neuropathic pain group (group DP),and by less than 25 ％ of the baseline were allocated to diabetic non-neuropathic pain group (group NP).The rats were sacrificed at 21 days after STZ injection,and their lumbar enlargements of the spinal cord were removed for determination of the expression of mTOR and phosphorylated mTOR (p-mTOR) by Western blot.Results The expression of mTOR was significantly up-regulated in DP and NP groups when compared with group C (P ＜ 0.05),the expression of p-mTOR was up-regulated in DP group,and no significant change was found in the expression of p-mTOR in group NP (P ＞ 0.05).Compared with group NP,the expression of p-mTOR was significantly up-regulated (P ＜ 0.05),and no significant change was found in the expression of mTOR in group DP (P ＞ 0.05).Conclusion Activation of mTOR in the spinal cord is involved in the development of diabetic neuropathic pain in rats. Key words: Receptor-interacting protein serine-threonine kinases; Diabetic neuropathies