Water-soluble lipopolymer delivery of N-methyl-D-aspartic acid receptor 2B siRNA relieves chronic neuropathic pain in rats

作     者：Jianhua Lu Yuanxiang Tao Xue Yang Weifeng Tu Hao Chen Jiaxiang Xiong Chungui Hu 

作者机构：Department of Anesthesiology Guangzhou General Hospital of Guangzhou Military Command of Chinese PLA Guangzhou 510010 Guangdong Province China Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore Maryland 21205 USA Department of Physiology Third Military Medical University Chongqing 400038 China 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2011年第6卷第29期

页      面：2279-2283页

核心收录：

学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 1002[医学-临床医学] 081704[工学-应用化学] 1001[医学-基础医学(可授医学、理学学位)] 07[理学] 08[工学] 0817[工学-化学工程与技术] 071006[理学-神经生物学] 

基　　金：the Natural Science Foundation of Guangdong Province,No.07000059 the Science and Technology Development Program of Guangzhou,No.2010Y1-C301 the Science and Technology Development Program of Guangdong Province,No.2010B031600123 

主　　题：water soluble lipopolymer N-Methyl-D-aspartic acid receptor 2B small interfering RNA peripheral nerve injury neuropathic pain 

摘      要：Spinal dorsal horn N-Methyl-D-aspartic acid receptor 2B （NR2B） overexpression plays an important role in the production and maintenance of neuropathic pain. Because small interfering RNA （siRNA） can inhibit NR2B expression, siRNA may provide a novel approach to treat neuropathic pain and possibly nerve injury. However, an efficient and safe vector for NR2B siRNA has not been discovered. This study shows that a water soluble lipopolymer （WSLP） comprised of low molecular weight polyethyleneimine （PEI） and cholesterol can deliver siRNA targeting NR2B for the treatment of neuropathic pain. Results show that intrathecal injection of WSLP/siRNA complexes for 3 days inhibit NR2B gene expression with reductions in mRNA and protein levels by 59% and 54%, respectively, compared with control rats （P 〈 0.01）. Injection of WSLP complexed with scrambled siRNA, or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly relieved neuropathic pain at 3, 7, 12, and 21 days, while injection of WSLP with scrambled siRNA or PEI with siRNA did not. These results demonstrate that WSLP can efficiently deliver siRNA targeting NR2B in vivo and relieve neuropathic pain.