Role of hippocampal mammalian target of rapamycin signaling pathway in inflammatory pain in rats

Abstract

Objective To evaluate the role of hippocampal mammalian target of rapamycin (mTOR) signaling pathway in inflammatory pain in rats. Methods Sixty adult male Sprague-Dawley rats, weighing 180-240 g, were randomly divided into 4 groups (n=6 each) by using a random number table: control group (group C), inflammatory pain group (group IP), dimethyl sulfoxide (DMSO) group and rapamycin (inhibitor of mTOR) group (group R). Inflammatory pain was produced by injection of honey bee venom 50 μl into the plantar surface of the left hindpaw.While the equal volume of normal saline was given instead in group C. In group D, 2% DMSO was injected through a gastric tube into stomach 1 ml per day lasting for 3 days, and inflammatory pain was produced at 1 h after the last injection on 3rd day.In group R, rapamycin 10 mg/kg (in 2% DMSO) was injected through a gastric tube into stomach 1 ml per day lasting for 3 days, and inflammatory pain was produced at 1 h after the last injection on 3rd day.At 2 h after the model was established, the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.Rats were sacrificed after measurement of pain threshold, and hippocampal tissues were obtained for detection of the expression of mTOR, phosphorylated mTOR (p-mTOR), ribosomal S6 kinase (S6K) and phosphorylated S6K (p-S6K). Results Compared to group C, the MWT was significantly decreased, TWL was shortened, the expression of p-mTOR and p-S6K was up-regulated, and no significant change was found in the expression of mTOR and S6K in IP and DMSO groups, and no significant change was found in group R in the MWT, TWL and expression of p-mTOR, mTOR, p-S6K and S6K.Compared to group IP, no significant change was found in group DMSO in the MWT, TWL and expression of p-mTOR, mTOR, p-S6K and S6K, and the MWT was significantly increased, TWL was prolonged, the expression of p-mTOR and p-S6K was down-regulated, and no significant change was found in the expression of mTOR and S6K in group R. Conclusion Hippocampal mTOR signaling pathways are involved in the development of inflammatory pain in rats. Key words: Receptor-interacting protein serine-threonine kinases; Hippocampus; Pain; Inflammation