ArticleBrain : a journal of neurology2019
A causal role for TRESK loss of function in migraine mechanisms.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 67 citations in OpenAlex.
- A highly efficient method to differentiate CGRP-expressing peptidergic nociceptors from human induced pluripotent stem cells.Stem cell reports · 2026Article
- Evaluation of Novel Cloxyquin Analogs for KArchiv der Pharmazie · 2026Article
- Cloxiquine exerts bactericidal activity against Enterococcus faecalis through disruption of proton motive force and induction of reactive oxygen species.BMC microbiology · 2026Article
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Calcium-dependent activation of TREK-1 and TREK-2 background potassium channels by calcineurin.Scientific reports · 2025Article
- Decoding Pain: Next-Generation In Vitro Systems for Mechanistic Insights and Drug Discovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Migraine with and without aura-two distinct entities? A narrative review.The journal of headache and pain · 2025Review
- Migraine is a dysfunction of neuronal potassium ion channels.Frontiers in neurology · 2025Review
- The Ubiquitin Ligase Adaptor NDFIP1 Interacts with TRESK and Negatively Regulates the Background KInternational journal of molecular sciences · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- Increased presynaptic excitability in a migraine with aura mutation.Brain : a journal of neurology · 2024Article
- Ion Channel Disturbances in Migraine Headache: Exploring the Potential Role of the Kynurenine System in the Context of the Trigeminovascular System.International journal of molecular sciences · 2023Review
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- Cloxyquin activates hTRESK by allosteric modulation of the selectivity filter.Communications biology · 2023Article
- Genetics of migraine: where are we now?The journal of headache and pain · 2023Review
- Towards bridging the translational gap by improved modeling of human nociception in health and disease.Pflugers Archiv : European journal of physiology · 2022Review
- Global analyses of mRNA expression in human sensory neurons reveal eIF5A as a conserved target for inflammatory pain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Peripheral Ion Channel Gene Screening in Painful- and Painless-Diabetic Neuropathy.International journal of molecular sciences · 2022Article
- Sphingosine-1 phosphate receptor 1 contributes to central sensitization in recurrent nitroglycerin-induced chronic migraine model.The journal of headache and pain · 2022Article
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Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
The two-pore potassium channel, TRESK has been implicated in nociception and pain disorders. We have for the first time investigated TRESK function in human nociceptive neurons using induced pluripotent stem cell-based models. Nociceptors from migraine patients with the F139WfsX2 mutation show loss of functional TRESK at the membrane, with a corresponding significant increase in neuronal excitability. Furthermore, using CRISPR-Cas9 engineering to correct the F139WfsX2 mutation, we show a reversal of the heightened neuronal excitability, linking the phenotype to the mutation. In contrast we find no change in excitability in induced pluripotent stem cell derived nociceptors with the C110R mutation and preserved TRESK current; thereby confirming that only the frameshift mutation is associated with loss of function and a migraine relevant cellular phenotype. We then demonstrate the importance of TRESK to pain states by showing that the TRESK activator, cloxyquin, can reduce the spontaneous firing of nociceptors in an in vitro human pain model. Using the chronic nitroglycerine rodent migraine model, we demonstrate that mice lacking TRESK develop exaggerated nitroglycerine-induced mechanical and thermal hyperalgesia, and furthermore, show that cloxyquin conversely is able to prevent sensitization. Collectively, our findings provide evidence for a role of TRESK in migraine pathogenesis and its suitability as a therapeutic target.
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