RT Journal Article SR Electronic T1 TRESK K+ Channel Activity Regulates Trigeminal Nociception and Headache JF bioRxiv FD Cold Spring Harbor Laboratory SP 679530 DO 10.1101/679530 A1 Zhaohua Guo A1 Chang-Shen Qiu A1 Xinhua Jiang A1 Jintao Zhang A1 Fengxian Li A1 Qin Liu A1 Ajay Dhaka A1 Yu-Qing Cao YR 2019 UL http://biorxiv.org/content/early/2019/06/21/679530.abstract AB Although dominant-negative mutations of TRESK background K+ channel have been reported in migraine patients, whether TRESK activity controls the generation of trigeminal pain, especially headache, is not established. We found that loss of TRESK in all trigeminal ganglia (TG) neurons preferentially increased the intrinsic excitability of small-diameter TG nociceptors that express neuropeptide CGRP or TRPM8 channels. Surprisingly, loss of TRESK increased the number of TG neurons expressing TRPV1 channels. In dorsal root ganglia neurons, neither the persistent outward current nor the intrinsic excitability was affected by the loss of TRESK. Compared with wild-type controls, TRESK knockout mice exhibited more robust trigeminal pain, especially headache-like behaviors; but displayed normal body and visceral pain responses. Our findings indicate that endogenous TRESK activity is required for trigeminal pain regulation. A substantial reduction of TRESK activity may selectively affect the functions of TG nociceptors, thereby increasing the susceptibility to migraine headache in humans.