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 Tet1^flox/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.

三叉神经炎性疼痛是人类最严重的疼痛相关疾病之一；然而，其根本机制仍然很大程度上未知。在这项研究中，我们研究了 10-11 易位甲基胞嘧啶双加氧酶 1 (TET1) 和电压门控 K ^{+通道 Kv7.2（由}Kcnq2编码）之间的相互作用对小鼠口面部炎性疼痛的可能影响。我们发现完全弗氏佐剂（CFA）注射降低了三叉神经节（TG）中Kcnq2 /Kv7.2的表达并诱发口面部炎性疼痛。Kv7.2 敲低或过表达进一步证实 Kv7.2 参与 CFA 诱导的口面部疼痛。此外，Tet1 ^flox/flox小鼠中 TET1 敲低显着降低了 TG 中 Kv7.2 和 M 电流的表达，并导致疼痛样行为。相反，慢病毒过表达 TET1 可以挽救 CFA 诱导的Kcnq2和 M 电流降低，并减轻机械性异常性疼痛。我们的数据表明，TET1 通过正向调节 TG 神经元中的 Kv7.2 与 CFA 诱导的三叉神经炎性疼痛有关。