Small interfering RNA-mediated knockdown of NF-¦ÊBp65 attenuates neuropathic pain following peripheral nerve injury in rats

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• 作者：Tao Sun^a ; ^{suntaosdph@163.com} ; Jiangang Luo^a ; ^{531274219@qq.com} ; Mingrui Jia^a ; ^{sydneyhuangxiaohe@163.com} ; Hui Li^a ; ^{1522177393@qq.com} ; Kezhong Li^b ; ^{ke_zhongli@163.com} ; Zhijian Fu^a ; ^{zhi_jianfu@163.com}
• 关键词：Lentiviral ; RNA interference ; NF-¦ÊBp65 ; Chronic constriction injury
• 刊名：European Journal of Pharmacology
• 出版年：2012
• 出版时间：5 May, 2012
• 年：2012
• 卷：682
• 期：1-3
• 页码：79-85
• 全文大小：884 K

文摘

Recent reports show that the nuclear factor-¦ÊB (NF-¦ÊB) can control numerous genes encoding inflammatory and nociceptive mediators and play an important role in the development of central pain sensitization. The aim of the present study is to assess the role of NF-¦ÊB signal pathway and its downstream pro-inflammatory cytokines in the modulation of neuropathic pain, by using small interfering RNAs (siRNAs) technique, which has been shown to result in potent, long-lasting post-transcriptional silencing of specific genes. We developed a highly efficient method of lentivirus-mediated delivery of short-hairpin RNA (shRNA) targeting NF-¦ÊBp65 for gene silencing. This method successfully transduced LV-shNF-¦ÊBp65 into cultured spinal cord neurons in vitro and spinal cord cells in vivo, inhibited the expression of NF-¦ÊBp65 and pro-inflammatory factors (TNF-¦Á, IL-1¦Â and IL-6) and alleviated mechanical allodynia and thermal hyperalgesia for more than 4 weeks in chronic constriction injury (CCI) model of rats. Taken together, our results suggest that siRNA against NF-¦ÊBp65 is a potential strategy for analgesia. Furthermore, the lentiviral vector derived shRNA approach shows a great promise for the management of neuropathic pain and the study of functional NF-¦ÊBp65 gene expression.