Effect of intraperitoneal WSLP/NR2B siRNA compound on neuropathic pain in rats

Abstract

Objective To evaluate the effect of intraperitoneal water soluble lipopolymer (WSLP)/ N-methyl-D-aspartate receptor subunit 2B (NR2B) siRNA compound on the neuropathic pain (NP) in rats.Methods Eighty-four healthy male Sprague-Dawley rats,aged 6 weeks,weighing 180-220 g,were randomly divided into 7 groups (n =12 each) using a random number table:control group (group C),sham operation group (group S),NP group,WSLP/NR2B siRNA group (siWSLP group),WSLP/negative control siRNA group (ncWSLP group),PEI/NR2B siRNA group (PEI group) and WSLP group (WSLP group).NP was produced by ligation of the left L5 spinal nerve.In group S,the left L5 spinal nerve was only exposed,but not ligated.In group C,the rats underwent no treatment.Groups siWSLP,ncWSLP,PEI and WSLP received single intraperitoneal injection of WSLP/NR2B siRNA,WSLP/negative control siRNA,PEI/NR2B siRNA and WSLP compound 2 ml,respectively,at 10 days after NP.At 1 day before operation,7 days after operation,and 3,7,14 and 21 days after intraperitoneal injection,6 rats in each group were chosen randomly to measure mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL).At 3 days after intraperitoneal injection,the left 6 rats in each group were sacrificed and the spinal cord was removed for detection of NP2B mRNA expression (using PCR) and NR2B expression (by Western blot).Results Compared with group C,MWT was significantly decreased,and TWL was shortened on 7 days after operation and 3,7 and 21 days after intraperitoneal injection,and the expression of NR2B mRNA and protein was down-regulated on 3 days after administration in the other groups.Compared with group NP,MWT was significantly increased,and TWL was prolonged on day 3 and 7 after intraperitoneal injection,and the expression of NR2B mRNA and protein was down-regulated on day 3 after administration in siWSLP group.Conclusion Intraperitoneal WSLP/NR2B siRNA compound can effectively relieve the NP in rats. Key words: Gene therapy; Transfection ; RNA, small interfering; Receptors, N-methyl-D-aspartate ; Neuralgia; Injections,intraperitoneal