TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model
Dengcheng Zhan1,2 · Jingjing Zhang1,2 · Songxue Su1 · Xiuhua Ren1 · Sen Zhao1,2 · Weidong Zang1,2 · Jing Cao1,21 Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
2 Neuroscience Research Institute, Zhengzhou University, Zhengzhou 450001, China
Abstract
Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans; however, the underlying mechanisms remain largely unknown. In this study, we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and the voltage-gated K+ channel Kv7.2 (encoded by Kcnq2) to orofacial inflammatory pain in mice. We found that complete Freund’s adjuvant (CFA) injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion (TG) and induced orofacial inflammatory pain. The involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or overexpression. Moreover, TET1 knockdown in Tet1flox/flox mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like behaviors. Conversely, TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical allodynia. Our data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.
Keywords
Facial pain; KCNQ2 potassium channel; TET1 protein
