Role of mammlian target of rapamycin signaling pathway in spinal cord in development of neuropathic pain in rats

Abstract

Objective To investigate the role of mammlian target of rapamycin (mTOR) signaling pathway in the spinal cord in the development of neuropathic pain (NP) in rats.Methods Twenty adult male SpragueDawley rats,weighing 180-220 g,were randomly divided into d groups (n =5 each) using a random number table:control group (group C),sham operation group (group S),NP group,and rapamycin group (group R).Intrathecal catheters were successfully implanted in the rats except those in group C and observed for 3 days.In group S,the left sciatic nerve was only exposed but not ligated.NP was produced by clamping the left sciatic nerve.In group R,rapamycin 10 μl was injected intrathecally at 4 h after NP for 3 consecutive days.At 1 day before operation and 3,5 and 7 days after NP,the mechanical pain threshold (MPT) was measured and the changes in synaptic structure and organelles in the 1amine Ⅱ of the spinal dorsal horn were studied with transmission electron microscope and stereological analysis.Results Compared with C and S groups,MPT was significantly decreased,the numerical density of all synapses,spine synapses,negative synapses and perforated synapses,thickness of the postsynaptic density and curvature of the synaptic interface were increased at 5 and 7 days after ligation in NP and R groups (P ＜ 0.05 or 0.01).Compared with NP group,MPT was significantly increased,the numerical density of all synapses,spine synapses,negative synapses and perforated synapses,thickness of the postsynaptic density and curvature of the synaptic interface were decreased at 5 and 7 days after ligation in R group (P ＜ 0.05).Conclusion mTOR signaling pathway in the spinal cord is involved in the development of NP in rats possibility through regulating synaptic plasticity in the spinal dorsal horn. Key words: Spinal cord; Receptor-interacting protein serine-threonine kinases; Neuralgia