title: A novel analgesic approach to optogenetically and specifically inhibit pain transmission using TRPV1 promoter.
abstract: 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.
authors: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
authors: Bei
authors: B
authors: Li
authors: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
authors: Xiang-Yu
authors: XY
authors: Yang
authors: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China.
authors: Fu-Ping
authors: FP
authors: Qian
authors: College of Biology and Environmental Sciences, Jishou University, Jishou, China.
authors: Min
authors: M
authors: Tang
authors: Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences; School of Basic Medicine, Peking Union Medical College, Department of Anatomy, Histology and Embryology, Beijing, China; School of Basic Medicine, Department of Anatomy, Histology and Embryology, Peking Union Medical College, Beijing, China. Electronic address: mcpumc@163.com.
authors: Chao
authors: C
authors: Ma
authors: The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, China. Electronic address: liyang.chiang@gmail.com.
authors: Li-Yang
authors: LY
authors: Chiang
mesh_terms: D000818:Animals; D019843:Archaeal Proteins / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics; D005727:Ganglia, Spinal / Q000378:metabolism; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D055352:Halorubrum; D006358:Hot Temperature; D006801:Humans; D007834:Lasers; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000378:metabolism; D062308:Optogenetics / Q000379:methods*; D010146:Pain / Q000378:metabolism; D059408:Pain Management / Q000379:methods*; D017288:Pain Threshold / Q000502:physiology; D011401:Promoter Regions, Genetic; D050916:TRPV Cation Channels / Q000235:genetics*; D014110:Touch; D017494:Proton Pumps
chemical_list: D019843:Archaeal Proteins; D049452:Green Fluorescent Proteins; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C055476:archaerhodopsin protein, Archaea; D017494:Proton Pumps; C485184:enhanced green fluorescent protein
keywords: Analgesic; ArchT; Nociceptor; Optogenetic; Pain; TRPV1