Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo
Silencing of vanilloid receptor TRPV1 by RNAi reduces neuropathic and visceral pain in vivo
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DOI：
10.1016/j.bbrc.2006.09.037
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发表时间：
2006-11-10
影响因子：
3.1
通讯作者：
Kurreck, Jens
中科院分区：
文献类型：
--
作者：
Christoph, Thomas;Gruenweller, Arnold;Kurreck, Jens
RNA干扰（RNAi）已被证明是一种强大的技术来研究基因的功能，通过产生敲低表型。在这里，我们报告说，鞘内注射的siRNA对瞬时受体电位香草酸受体I（TRPV1）减少冷异常性疼痛的单神经病大鼠超过50%，在一段时间内约5天。采用靶向TRPV1基因的不同区域的第二siRNA，并证实了TRPV1敲低的镇痛作用。此外，siRNA治疗减少了由辣椒素应用于小鼠直肠诱导的自发内脏疼痛行为。siRNA介导的TRPV1敲低在内脏痛模型中的镇痛作用与低分子量受体拮抗剂BCTC相当。我们的数据表明，TRPV1拮抗剂，包括TRPV1 siRNA，在治疗神经性疼痛和内脏疼痛方面具有潜力。(c)2006年爱思唯尔公司All rights reserved.
RNA interference (RNAi) has proven to be a powerful technique to study the function of genes by producing knock-down phenotypes. Here, we report that intrathecal injection of an siRNA against the transient receptor potential vanilloid receptor I (TRPV1) reduced cold allodynia of mononeuropathic rats by more than 50% over a time period of approximately 5 days. A second siRNA targeted to a different region of the TRPV1 gene was employed and confirmed the analgesic action of a TRPV1 knock-down. Furthermore, siRNA treatment diminished spontaneous visceral pain behavior induced by capsaicin application to the rectum of mice. The analgesic effect of siRNA-mediated knockdown of TRPV1 in the visceral pain model was comparable to that of the low-molecular weight receptor antagonist BCTC. Our data demonstrate that TRPV1 antagonists, including TRPV1 siRNAs, have potential in the treatment of both, neuropathic and visceral pain. (c) 2006 Elsevier Inc. All rights reserved.