The Interventional Effect Of PSD-95Gene Silencing On Behavioral Changes In Rats With Neuropathic Pain

Objective:It is taught that PSD-95is involved in the generation and development of chronic neuropathic pain. RNAi (RNA interference) technique and small interfering RNA (siRNA) now offer a powerful and highly specific tool for therapeutic gene silencing. The aim of this study is to investigate the efficiency of PSD-95gene silencing by siRNA, together with its therapeutic effect on chronic constriction injury model rats.Methods:Ninety-six male SD rats, weighting200-250g were randomly divided into6groups (n=5for each group):Naive, Sham(sham3d and sham7d), CCI(CCI3d, CCI7d and CCI14d). Mechanical allodynia and thermal hyperalgesia were measured to evaluate the success of the model. The rats were executed on3rdd、7thd、14thd after the surgery, and the level of PSD-95mRNA was compared among each group. Then the proper length of the catheter, rat body weight, and the agent dosage were preliminarily evaluated for intrathecal administration. PSD-95siRNA(2μg/d X4d), saline, i-FectTM or control siRNA was given intrathecally(i.t). Mechanical allodynia and thermal hyperalgesia were measured to evaluate the analgesic effect of PSD-95siRNA. On the1st day and5th day after the last administration, rats were sacrificed and lumbar spinal cords were sampled for further real-time PCR analysis.Results:Chronic constriction injury of rat sciatic nerve produced a clear-cut mechanical allodynia and thermal hyepralgesia in rats submitted to the surgery compared to the sham operated and naive ones. Intrathecal PSD-95siRNA (2μg/d X3d, i.t.) could significantly reduce the level of PSD-95mRNA in the spinal cord, and intrathecal PSD-95siRNA (2μg/dX4d, i.t.) could elevate the mechanical withdrawal threshold and paw withdrawal thermal latency of CCI rats without affecting the baseline antinociception.Conclusion:The PSD-95mRNA level exhibited no chage in the superficial dorsal horn after chronic constriction injury of rat sciatic nerve. In vivo delivery of PSD-95siRNA using i-FectTM could significantly silent the target gene, as relieved neuropathic pain in CCI model rats.