文章基本信息

标题：TREK channel activation suppresses migraine pain phenotype
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作者：Pablo Ávalos Prado ; Arnaud Landra-Willm ; Clément Verkest 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-14
DOI：10.1016/j.isci.2021.102961
语种：English
出版社：Elsevier
摘要：SummaryActivation 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 invalidationex vivoandin vivo, we demonstrate that activating TREK1 and TREK2 two-pore-domain potassium (K2P) 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.Graphical abstractDisplay OmittedHighlights•Trek1andTrek2invalidation increases TG excitability and generates migraine•TREK1 and TREK2 activation prevents migraine in rodents•TREK1/TREK2 agonists are as good as the most efficient current cares for migraine•Targeting TREK channels needs to be considered for clinical treatment on migrainePharmacology; Biological sciences; Neuroscience; Behavioral neuroscience; Sensory neuroscience