PT  - JOURNAL ARTICLE
AU  - Zhaohua Guo
AU  - Chang-Shen Qiu
AU  - Xinhua Jiang
AU  - Jintao Zhang
AU  - Fengxian Li
AU  - Qin Liu
AU  - Ajay Dhaka
AU  - Yu-Qing Cao
TI  - TRESK K<sup>+</sup> Channel Activity Regulates Trigeminal Nociception and Headache
AID  - 10.1101/679530
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 679530
4099  - http://biorxiv.org/content/early/2019/06/21/679530.short
4100  - http://biorxiv.org/content/early/2019/06/21/679530.full
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.