Open AccessConnexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1
Author(s) -
Qian Li,
Tianle Ma,
You-Qi Qiu,
Weihong Cui,
Teng Chen,
Wenwen Zhang,
Jing Wang,
Qi-Liang Mao-Ying,
Wen-Li Mi,
Yan-Qing Wang,
YuXia Chu
Publication year - 2020
Publication title -
neuroscience bulletin/neuroscience bulletin
Language(s) - English
Resource type - Journals
eISSN - 1673-7067
pISSN - 1995-8218
DOI - 10.1007/s12264-020-00594-4
Subject(s) - allodynia , trigeminal ganglion , medicine , orofacial pain , neuropathic pain , pharmacology , anesthesia , nociception , chemistry , neuroscience , endocrinology , hyperalgesia , receptor , biology , surgery , sensory system
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.