PMID- 31308053
OWN - NLM
STAT- MEDLINE
DCOM- 20200306
LR  - 20200309
IS  - 2373-2822 (Electronic)
IS  - 2373-2822 (Linking)
VI  - 6
IP  - 4
DP  - 2019 Jul/Aug
TI  - TRESK K(+) Channel Activity Regulates Trigeminal Nociception and Headache.
LID - ENEURO.0236-19.2019 [pii]
LID - 10.1523/ENEURO.0236-19.2019 [doi]
AB  - Although TWIK-related spinal cord K(+) (TRESK) channel is expressed in all 
      primary afferent neurons in trigeminal ganglia (TG) and dorsal root ganglia 
      (DRG), whether TRESK activity regulates trigeminal pain processing is still not 
      established. Dominant-negative TRESK mutations are associated with migraine but 
      not with other types of pain in humans, suggesting that genetic TRESK dysfunction 
      preferentially affects the generation of trigeminal pain, especially headache. 
      Using TRESK global knock-out mice as a model system, we found that loss of TRESK 
      in all TG neurons selectively increased the intrinsic excitability of 
      small-diameter nociceptors, especially those that do not bind to isolectin B4 
      (IB4(-)). Similarly, loss of TRESK resulted in hyper-excitation of the small 
      IB4(-) dural afferent neurons but not those that bind to IB4 (IB4(+)). Compared 
      with wild-type littermates, both male and female TRESK knock-out mice exhibited 
      more robust trigeminal nociceptive behaviors, including headache-related 
      behaviors, whereas their body and visceral pain responses were normal. 
      Interestingly, neither the total persistent outward current nor the intrinsic 
      excitability was altered in adult TRESK knock-out DRG neurons, which may explain 
      why genetic TRESK dysfunction is not associated with body and/or visceral pain in 
      humans. We reveal for the first time that, among all primary afferent neurons, TG 
      nociceptors are the most vulnerable to the genetic loss of TRESK. Our findings 
      indicate that endogenous TRESK activity regulates trigeminal nociception, likely 
      through controlling the intrinsic excitability of TG nociceptors. Importantly, we 
      provide evidence that genetic loss of TRESK significantly increases the 
      likelihood of developing headache.
CI  - Copyright (c) 2019 Guo et al.
FAU - Guo, Zhaohua
AU  - Guo Z
AD  - Washington University Pain Center, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
FAU - Qiu, Chang-Shen
AU  - Qiu CS
AD  - Washington University Pain Center, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
FAU - Jiang, Xinghua
AU  - Jiang X
AD  - Washington University Pain Center, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
FAU - Zhang, Jintao
AU  - Zhang J
AD  - Washington University Pain Center, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
FAU - Li, Fengxian
AU  - Li F
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
AD  - Center for the Study of Itch, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
FAU - Liu, Qin
AU  - Liu Q
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
AD  - Center for the Study of Itch, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
FAU - Dhaka, Ajay
AU  - Dhaka A
AD  - Department of Biological Structure, Neurobiology and Behavior Graduate Program, 
      University of Washington, Seattle, Washington 98195.
FAU - Cao, Yu-Qing
AU  - Cao YQ
AD  - Washington University Pain Center, Washington University School of Medicine, St. 
      Louis, Missouri 63110 Caoy@anest.wustl.edu.
AD  - Department of Anesthesiology, Washington University School of Medicine, St. 
      Louis, Missouri 63110.
LA  - eng
GR  - R01 NS083698/NS/NINDS NIH HHS/United States
GR  - R01 NS103350/NS/NINDS NIH HHS/United States
GR  - R21 NS087321/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190729
PL  - United States
TA  - eNeuro
JT  - eNeuro
JID - 101647362
RN  - 0 (Potassium Channels)
RN  - 0 (Trik protein, mouse)
SB  - IM
MH  - Animals
MH  - Female
MH  - Ganglia, Spinal/physiopathology
MH  - Headache/*physiopathology
MH  - Male
MH  - Membrane Potentials
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons, Afferent/metabolism/*physiology
MH  - Nociception/*physiology
MH  - Nociceptors/physiology
MH  - Pain/*physiopathology
MH  - Potassium Channels/genetics/metabolism/*physiology
MH  - Trigeminal Ganglion/metabolism/*physiopathology
PMC - PMC6664143
OTO - NOTNLM
OT  - TRESK
OT  - headache
OT  - intrinsic excitability
OT  - primary afferent neuron
OT  - trigeminal ganglion
OT  - trigeminal pain
EDAT- 2019/07/17 06:00
MHDA- 2020/03/07 06:00
PMCR- 2019/07/26
CRDT- 2019/07/17 06:00
PHST- 2019/06/20 00:00 [received]
PHST- 2019/06/23 00:00 [accepted]
PHST- 2019/07/17 06:00 [pubmed]
PHST- 2020/03/07 06:00 [medline]
PHST- 2019/07/17 06:00 [entrez]
PHST- 2019/07/26 00:00 [pmc-release]
AID - ENEURO.0236-19.2019 [pii]
AID - eN-NWR-0236-19 [pii]
AID - 10.1523/ENEURO.0236-19.2019 [doi]
PST - epublish
SO  - eNeuro. 2019 Jul 29;6(4):ENEURO.0236-19.2019. doi: 10.1523/ENEURO.0236-19.2019. 
      Print 2019 Jul/Aug.