Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice  

作　　者：Seong-Ah Kim Jun Ho Jang Wheedong Kim Pa Reum Lee Yong Ho Kim Hue Vang Kihwan Lee Seog Bae Oh 

机构地区：[1]Department of Neurobiology and Physiology,School of Dentistry and Dental Research Institute,Seoul National University,Seoul 03080,Republic of Korea [2]Department of Brain and Cognitive Sciences,College of Natural Sciences,Seoul National University,Seoul 08826,Republic of Korea [3]Gachon Pain Center and Department of Physiology,College of Medicine,Gachon University,Incheon 21999,Republic of Korea [4]Tooth-Periodontium Complex Medical Research Center,School of Dentistry,Seoul National University,Seoul 03080,Republic of Korea

出　　处：《Neuroscience Bulletin》2022年第4期373-385,共13页神经科学通报（英文版）

基　　金：supported by the National Research Foundation(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2018R1A5A2024418 and NRF-2021R1A2C3003334);the Basic Science Research Program through the NRF funded by the Ministry of Education(NRF-2020R1I1A1A01068037).

摘　　要：Mitochondrial reactive oxygen species(mROS)that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities.Here,we explored whether mROS overproduction induces itch through transient receptor potential canonical 3(TRPC3),which is sensitive to ROS.Intradermal injection of antimycin A(AA),a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction,produced robust scratching behavior in naïve mice,which was suppressed by MitoTEMPO,a mitochondria-selective ROS scavenger,and Pyr10,a TRPC3-specific blocker,but not by blockers of TRPA1 or TRPV1.AA activated subsets of trigeminal ganglion neurons and also induced inward currents,which were blocked by MitoTEMPO and Pyr10.Besides,dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10,and also by resveratrol,an antioxidant.Taken together,our results suggest that mROS elicit itch through TRPC3,which may underlie chronic itch,representing a potential therapeutic target for chronic itch.

关 键 词：MITOCHONDRIA Reactive oxygen species TRPC3 ITCH Dry skin Trigeminal ganglia 

分 类 号：R338[医药卫生—人体生理学]