Underlying Mechanisms Of NR2B-Reg-2Signaling Axis In Rat Neuropathic Pain

Objective:To investigate the analgesic effect of NR2B antagonist ifenprodil on chronicconstriction injury (CCI)-induced neuropathic pain in the sciatic nerve of rats andpotential regulatory machanism of Reg-2-NR2B signaling axis underlyingneuropathic pain pathogenesis.Methods:A total108male SD rats (180g~200g) were randomly assigned into3groups:sham operation group (n=36), CCI group (n=36), and ifenprodil group (n=36). Sciaticnerve was ligated or not in CCI group and sham group, respectively. Ifenprodil wasgiven daily via intraperitoneal injection (10mg/kg) in ifenprodil group while dimethylsulfoxide of equalvolume was injected in other groups. Mechanical pain threshold wasmeasured by paw withdrawal latencies to von Frey hair in the experimental rats andthen they were sacrificed on day1before operation and day1,3,5, and7afteroperation. L4-6segments of spinal cord was resected for determination of expressionof NR2B and Reg-2at mRNA (RT-qPCR) and protein (immuno-histochemistry andwestern-bolt) levels.Results:There was no significant differences of mechanical pain threshold measuredpreoperatively among all the three groups (P>0.05).CCI significantly decreased themechanical pain threshold and increased the expression of NR2B and Reg-2mRNAand protein day3after surgery and lasted from them on, as compared with shamgroup. Comparative study also suggested that ifenprodil treatment markedly elevatedthe mechanical pain threshold and downregulated the expression of NR2B and Reg-2mRNA and protein since its onset at day3after surgery.Conclusion:1. NR2B-Reg-2signaling axis involved in the generation and regulation ofneuropathic pain which induced by the CCI model. 2. Ifenprodil exserted significant analgesic effect on neuropathic pain which wasclosely associated with the alteration of NR2B-Reg-2signaling axis.