Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1  

作　　者：Qian Li Tian-Le Ma You-Qi Qiu Wen-Qiang Cui Teng Chen Wen-Wen Zhang Jing Wang Qi-Liang Mao-Ying Wen-Li Mi Yan-Qing Wang Yu-Xia Chu 

机构地区：[1]Department of Integrative Medicine and Neurobiology,Institutes of Integrative Medicine,School of Basic Medical Sciences,Institutes of Brain Science,Brain Science Collaborative Innovation Center,State Key Laboratory of Medical Neurobiology,and MOE Frontiers Center for Brain Science,Fudan University,Shanghai 200031,China [2]Department of Pain Management,Shandong Provincial Qianfoshan Hospital,The First Hospital Affiliated with Shandong First Medical University,Jinan 250000,China [3]Department of Nephropathy,The Third Affiliated Hospital of Shenzhen University,Luohu Hospital Group,Shenzhen 518001,China

出　　处：《Neuroscience Bulletin》2020年第12期1484-1499,共16页神经科学通报（英文版）

基　　金：the National Natural Science Foundation of China(81971056,31600852,81771202,and 81873101);the Innovative Research Team of Highlevel Local Universities in Shanghai;the Foundation of Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180302153701406);the National Key R&D Program of China(2017YFB0403803);the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01);ZJLab。

摘　　要：Trigeminal neuralgia is a debilitating condition,and the pain easily spreads to other parts of the face.Here,we established a mouse model of partial transection of the infraorbital nerve(pT-ION)and found that the Connexin 36(Cx36)inhibitor mefloquine caused greater alleviation of pT-ION-induced cold allodynia compared to the reduction of mechanical allodynia.Mefloquine reversed the pT-IONinduced upregulation of Cx36,glutamate receptor ionotropic kainate 2(GluK2),transient receptor potential ankyrin 1(TRPA1),and phosphorylated extracellular signal regulated kinase(p-ERK)in the trigeminal ganglion.Cold allodynia but not mechanic al allodynia induced by pT-ION or by virusmediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS 102,and knocking down Cx36 expression in Nav1.8-expressing nociceptors by injecting virus into the orofacial skin area of Nav1.8-Cre mice attenuated cold allodynia but not mechanic al allodynia.In conclusion,we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2,TRPA1,and p-ERK signaling.

关 键 词：Orofacial pain Gap junction Glutamate receptor ionotropic kainate 2 Transient receptor potential A1 

分 类 号：R745.11[医药卫生—神经病学与精神病学]