PMID- 34458705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210831
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 24
IP  - 9
DP  - 2021 Sep 24
TI  - TREK channel activation suppresses migraine pain phenotype.
PG  - 102961
LID - 10.1016/j.isci.2021.102961 [doi]
LID - 102961
AB  - Activation and sensitization of trigeminal ganglia (TG) sensory neurons, leading 
      to the release of pro-inflammatory peptides such as calcitonin gene-related 
      peptide (CGRP), are likely a key component in migraine-related headache 
      induction. Reducing TG neuron excitability represents therefore an attractive 
      alternative strategy to relieve migraine pain. Here by using pharmacology and 
      genetic invalidation ex vivo and in vivo, we demonstrate that activating TREK1 
      and TREK2 two-pore-domain potassium (K(2P)) channels inhibits TG neuronal firing 
      sufficiently to fully reverse the migraine-like phenotype induced by NO-donors in 
      rodents. Finally, targeting TREK is as efficient as treatment with CGRP 
      antagonists, which represents one of the most effective migraine therapies. 
      Altogether, our results demonstrate that inhibiting TG excitability by 
      pharmacological activation of TREK channels should be considered as an 
      alternative to the current migraine treatment.
CI  - (c) 2021 The Author(s).
FAU - Avalos Prado, Pablo
AU  - Avalos Prado P
AD  - Universite Cote d'Azur, CNRS, INSERM, iBV, Nice, France.
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
FAU - Landra-Willm, Arnaud
AU  - Landra-Willm A
AD  - Universite Cote d'Azur, CNRS, INSERM, iBV, Nice, France.
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
FAU - Verkest, Clement
AU  - Verkest C
AD  - Universite Cote d'Azur, CNRS, INSERM, iBV, Nice, France.
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, Valbonne, France.
FAU - Ribera, Aurore
AU  - Ribera A
AD  - Universite Cote d'Azur, CNRS, INSERM, iBV, Nice, France.
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
FAU - Chassot, Anne-Amandine
AU  - Chassot AA
AD  - Universite Cote d'Azur, CNRS, INSERM, iBV, Nice, France.
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
FAU - Baron, Anne
AU  - Baron A
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
AD  - Universite Cote d'Azur, CNRS, Institut de Pharmacologie Moleculaire et 
      Cellulaire, Valbonne, France.
FAU - Sandoz, Guillaume
AU  - Sandoz G
AD  - Universite Cote d'Azur, CNRS, INSERM, iBV, Nice, France.
AD  - Laboratories of Excellence, Ion Channel Science and Therapeutics, Nice, France.
AD  - Federation Hospitalo-Universitaire InovPain, Cote d'Azur University, University 
      Hospital Centre Nice, Nice, Provence-Alpes-Cote d'Azur, France.
LA  - eng
PT  - Journal Article
DEP - 20210808
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC8379698
OTO - NOTNLM
OT  - Sensory neuroscience
OT  - behavioral neuroscience
OT  - biological sciences
OT  - neuroscience
OT  - pharmacology
COIS- The authors declare no competing interest.
EDAT- 2021/08/31 06:00
MHDA- 2021/08/31 06:01
PMCR- 2021/08/08
CRDT- 2021/08/30 06:07
PHST- 2021/05/19 00:00 [received]
PHST- 2021/06/20 00:00 [revised]
PHST- 2021/08/04 00:00 [accepted]
PHST- 2021/08/30 06:07 [entrez]
PHST- 2021/08/31 06:00 [pubmed]
PHST- 2021/08/31 06:01 [medline]
PHST- 2021/08/08 00:00 [pmc-release]
AID - S2589-0042(21)00929-9 [pii]
AID - 102961 [pii]
AID - 10.1016/j.isci.2021.102961 [doi]
PST - epublish
SO  - iScience. 2021 Aug 8;24(9):102961. doi: 10.1016/j.isci.2021.102961. eCollection 
      2021 Sep 24.