Intrathecal Lentiviral-Mediated RNA Interference Targeting PKCγ Attenuates Chronic Constriction Injury-Induced Neuropathic Pain in Rats

In the spinal cord, protein kinase C isoform gamma (PKC gamma) plays an important role in the development of central pain sensitization. However, there are currently no specific PKC gamma inhibitors available. Therefore, the aim of the present study was to assess the role of PKC gamma 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 PKC gamma for in vivo gene silencing in the spinal cord of rats. This method decreased the expression of PKC gamma mRNA and protein, and additionally attenuated chronic constriction injury-induced mechanical allodynia and thermal hyperalgesia for more than 6 weeks. Our study suggests that PKC gamma 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 PKC gamma gene function.