Christoph Thomas, Grünweller Arnold, Mika Joanna, Schäfer Martin K-H, Wade Erik J, Weihe Eberhard, Erdmann Volker A, Frank Robert, Gillen Clemens, Kurreck Jens
Research and Development, Grünenthal GmbH, Aachen, Germany.
Biochem Biophys Res Commun. 2006 Nov 10;350(1):238-43. doi: 10.1016/j.bbrc.2006.09.037. Epub 2006 Sep 18.
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 1 (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.
RNA干扰（RNAi）已被证明是一种通过产生基因敲低表型来研究基因功能的强大技术。在此，我们报告，鞘内注射针对瞬时受体电位香草酸受体1（TRPV1）的小干扰RNA（siRNA），在大约5天的时间段内，可使单神经病大鼠的冷异常性疼痛降低超过50%。使用了靶向TRPV1基因不同区域的第二种siRNA，并证实了TRPV1基因敲低的镇痛作用。此外，siRNA治疗减少了辣椒素作用于小鼠直肠所诱导的自发性内脏疼痛行为。在内脏疼痛模型中，siRNA介导的TRPV1基因敲低的镇痛效果与低分子量受体拮抗剂BCTC相当。我们的数据表明，包括TRPV1 siRNA在内的TRPV1拮抗剂在治疗神经性疼痛和内脏疼痛方面均具有潜力。
