Intrathecal lentiviral-mediated RNA interference targeting PKCγ attenuates chronic constriction injury-induced neuropathic pain in rats.
Intrathecal lentiviral-mediated RNA interference targeting PKCγ attenuates chronic constriction injury-induced neuropathic pain in rats.
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DOI：
10.1089/hum.2010.207
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发表时间：
2011-02
影响因子：
4.2
通讯作者：
W. Zou;Zongbin Song;Q. Guo;Chang Liu;Zhong-tang Zhang;Yanfeng Zhang
中科院分区：
文献类型：
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作者：
W. Zou;Zongbin Song;Q. Guo;Chang Liu;Zhong-tang Zhang;Yanfeng Zhang
在脊髓中，蛋白激酶C亚型γ（PKCγ）在中枢疼痛敏感化的发展中起重要作用。然而，目前没有特异性PKCγ抑制剂可用。因此，本研究的目的是使用更具选择性的实验工具来评估PKCγ在疼痛调制中的作用。尽管小干扰RNA已被用于沉默神经元中的基因，但RNA干扰（RNAi）的体内递送仍然是一个主要挑战，从而限制了其应用。在这里，我们开发了一种高效的方法，慢病毒介导的递送靶向PKCγ的短发夹RNA，用于大鼠脊髓中的体内基因沉默。该方法降低了PKCγ mRNA和蛋白的表达，并且另外减轻了慢性压迫性损伤诱导的机械异常性疼痛和热痛觉过敏超过6周。我们的研究表明PKCγ是神经病理性疼痛的潜在RNAi靶点。此外，慢病毒载体递送策略作为治疗神经病理性疼痛和研究PKCγ基因功能的新方法具有很大的前景。
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.