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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This work was supported by the National Natural Science Foundation of China (81971056, 31600852, 81771202, and 81873101), the Innovative Research Team of High-level 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), and ZJLab.
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Li, Q., Ma, TL., Qiu, YQ. et al. Connexin 36 Mediates Orofacial Pain Hypersensitivity Through GluK2 and TRPA1. Neurosci. Bull. (2020). https://doi.org/10.1007/s12264-020-00594-4
- Orofacial pain
- Gap junction
- Glutamate receptor ionotropic kainate 2
- Transient receptor potential A1