Li Bei, Yang Xiang-Yu, Qian Fu-Ping, Tang Min, Ma Chao, Chiang Li-Yang
The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
College of Biology and Environmental Sciences, Jishou University, Jishou, China.
Brain Res. 2015 Jun 3;1609:12-20. doi: 10.1016/j.brainres.2015.03.008. Epub 2015 Mar 20.
Chronic pain is a pathological condition that results in significant loss of life quality, but so far no specific treatment for chronic pain has been developed. Currently available analgesia drugs are either not specific enough or have severe side effects. Therefore a non-invasive approach with high specificity to inhibit nociception becomes essential. In this study, a recombinant virus (AAV5-TRPV1-ArchT-eGFP) was constructed and injected into the mouse dorsal root ganglion (DRG). The Transient Receptor Potential Vanilloid type 1 (TRPV1) channel promoter was used to selectively express inhibitory light-sensitive pump ArchT (the archaerhodopsin from Halorubrum strain TP009) in nociceptive DRG neurons. The successful transfer of ArchT gene was confirmed by a robust expression of green florescent protein in the DRG neurons. In vivo behavioral tests demonstrated that both the mechanical paw withdrawal threshold and the radiant heat evoked paw withdrawal latency were significantly increased upon illumination by a 532 nm green laser light to the paw of a viral-vector injected mice, while the same laser light did not induce any observable change in naïve mice. In conclusion, we have established a novel analgesic approach that can noninvasively and selectively inhibit pain transmission using an acute and controllable optogenetics method. This study may shed light on the application of a novel optogenetic strategy for the treatment of pain.
慢性疼痛是一种导致生活质量显著下降的病理状态，但迄今为止尚未开发出针对慢性疼痛的特效治疗方法。目前可用的镇痛药物要么特异性不足，要么有严重的副作用。因此，一种具有高特异性的非侵入性抑制伤害感受的方法变得至关重要。在本研究中，构建了一种重组病毒（AAV5-TRPV1-ArchT-eGFP）并将其注射到小鼠背根神经节（DRG）中。使用瞬时受体电位香草酸亚型1（TRPV1）通道启动子在伤害性DRG神经元中选择性表达抑制性光敏泵ArchT（来自嗜盐红菌菌株TP009的古紫质）。通过DRG神经元中绿色荧光蛋白的强烈表达证实了ArchT基因的成功转移。体内行为测试表明，用532nm绿色激光照射注射病毒载体的小鼠的爪子时，机械性缩爪阈值和辐射热诱发的缩爪潜伏期均显著增加，而相同的激光照射对未处理的小鼠未引起任何可观察到的变化。总之，我们建立了一种新的镇痛方法，该方法可以使用急性且可控的光遗传学方法非侵入性地、选择性地抑制疼痛传递。本研究可能为一种新型光遗传学策略在疼痛治疗中的应用提供启示。
