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01-12-2020 | Mefloquine | Original Article

Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Authors: 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

Published in: Neuroscience Bulletin | Issue 12/2020

Abstract

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-ION-induced 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 mechanical allodynia induced by pT-ION or by virus-mediated overexpression of Cx36 in the trigeminal ganglion was reversed by the GluK2 antagonist NS102, 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 mechanical allodynia. In conclusion, we show that Cx36 contributes greatly to the development of orofacial pain hypersensitivity through GluK2, TRPA1, and p-ERK signaling.

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Title: Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1
Authors: 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
Publication date: 01-12-2020
Publisher: Springer Singapore
Keyword: Mefloquine
Published in: Neuroscience Bulletin / Issue 12/2020
Print ISSN: 1673-7067
Electronic ISSN: 1995-8218
DOI: https://doi.org/10.1007/s12264-020-00594-4

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Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1

Abstract

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Abstract

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