Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1.
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| 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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| 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 |
| Journal | Neuroscience bulletin (Neurosci Bull) Vol. 36 Issue 12 Pg. 1484-1499 (Dec 2020) ISSN: 1995-8218 [Electronic] Singapore |
| PMID | 33067780 (Publication Type: Journal Article) |
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