ReviewPflugers Archiv : European journal of physiology2015
Two-pore domain potassium channels: potential therapeutic targets for the treatment of pain.
Review in Pflugers Archiv : European journal of physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- Swapped and non-swapped TRAAK states co-exist in membranes at a ratio influenced by temperature.Nature communications · 2026Article
- Insights into the structure and modulation of human TWIK-2.Nature communications · 2026Article
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Quantum Mechanical Mechanisms in the Therapeutic Effects of Spinal Cord Stimulation to Treat Chronic Neuropathic Pain: A Quantum Computational Model.Journal of pain research · 2026Article
- The cornea-trigeminal axis: potassium channels as master regulators of ocular surface homeostasis and sensory transduction.Frontiers in cell and developmental biology · 2026Review
- Discovery of ONO-2920632 (VU6011887): A Highly Selective and CNS Penetrant TREK-2 (TWIK-Related K+ Channel 2) Preferring ActivatorACS chemical neuroscience · 2025Article
- Low-intensity pulsed ultrasound ameliorates partial infraorbital nerve ligation-induced trigeminal neuropathic pain through inhibiting Schwann cell Pannexin 1 channel.Frontiers in immunology · 2025Article
- Unraveling the Molecular Reason of Opposing Effects of α-Mangostin and Norfluoxetine on TREK-2 at the Same Binding Site.ChemMedChem · 2024Article
- Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- Article
- Norfluoxetine inhibits TREK-2 K2P channels by multiple mechanisms including state-independent effects on the selectivity filter gate.The Journal of general physiology · 2021Article
- Block of TREK and TRESK K2P channels by lamotrigine and two derivatives sipatrigine and CEN-092.Biochemistry and biophysics reports · 2021Article
- Contribution of K2P Potassium Channels to Cardiac Physiology and Pathophysiology.International journal of molecular sciences · 2021Review
- A "Target Class" Screen to Identify Activators of Two-Pore Domain Potassium (K2P) Channels.SLAS discovery : advancing life sciences R & D · 2021Article
- Pharmacological Approaches to Studying Potassium Channels.Handbook of experimental pharmacology · 2021Review
- Controlled Decompression Attenuates Compressive Injury following Traumatic Brain Injury via TREK-1-Mediated Inhibition of Necroptosis and Neuroinflammation.Oxidative medicine and cellular longevity · 2021Article
- Contribution of Neuronal and Glial Two-Pore-Domain Potassium Channels in Health and Neurological Disorders.Neural plasticity · 2021Review
- Improving NKCC1 Function Increases the Excitability of DRG Neurons Exacerbating Pain Induced After TRPV1 Activation of Primary Sensory Neurons.Frontiers in cellular neuroscience · 2021Article
- The Pharmacology of Two-Pore Domain Potassium Channels.Handbook of experimental pharmacology · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Recent evidence points to a pivotal contribution of a variety of different potassium channels, including two-pore domain potassium (K2P) channels, in chronic pain processing. Expression of several different K2P channel subunits has been detected in nociceptive dorsal root ganglion neurons and trigeminal ganglion neurons, in particular, TREK1, TREK2, TRESK, TRAAK, TASK3 and TWIK1 channels. Of these, the strongest body of evidence from functional studies highlights the importance of TREK1, TRESK and, recently, TREK2 channels. For example, TREK1 knockout mice are more sensitive than wild-type mice to a number of painful stimuli but less sensitive to morphine-induced analgesia. TRESK knockdown mice show behavioural evidence of increased pain and increased sensitivity to painful pressure. Importantly, familial migraine with aura is associated with a dominant-negative mutation in human TRESK channels. Thus, the functional up-regulation of K2P channel activity may be a useful strategy in the development of new therapies for the treatment of pain. Whilst there are few currently available compounds that selectively and directly enhance the activity of TRESK and TREK2 channels, recent advances have been made in terms of identifying compounds that activate TREK1 channels and in understanding how they might act on the channel. Large-scale bio-informatic approaches and the further development of databases of putative ligands, channel structures and putative ligand binding sites on these structures may form the basis for future experimental strategies to detect novel molecules acting to enhance K2P channel activity that would be useful in the treatment of pain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.