title: Intrathecal lentiviral-mediated RNA interference targeting PKCγ attenuates chronic constriction injury-induced neuropathic pain in rats.
abstract: In the spinal cord, protein kinase C isoform γ (PKCγ) plays an important role in the development of central pain sensitization. However, there are currently no specific PKCγ inhibitors available. Therefore, the aim of the present study was to assess the role of PKCγ in the modulation of pain using a more selective experimental tool. Although small interfering RNAs have been used to silence genes in neurons, in vivo delivery of RNA interference (RNAi) remains a major challenge, thus limiting its applications. Here we developed a highly efficient method of lentiviral-mediated delivery of short-hairpin RNAs targeting PKCγ for in vivo gene silencing in the spinal cord of rats. This method decreased the expression of PKCγ mRNA and protein, and additionally attenuated chronic constriction injury-induced mechanical allodynia and thermal hyperalgesia for more than 6 weeks. Our study suggests that PKCγ is a potential RNAi target for neuropathic pain. Furthermore, the lentiviral vector delivery strategy holds great promise as a novel approach for the treatment of neuropathic pain and study of PKCγ gene function.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Wangyuan
authors.initials: W
authors.lastname: Zou
authors.forename: Zongbin
authors.initials: Z
authors.lastname: Song
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D023061:Gene Order; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D007278:Injections, Spinal; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D014161:Transduction, Genetic
chemical_list: D034741:RNA, Small Interfering; C087857:protein kinase C gamma; D011493:Protein Kinase C