ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
TREK2 expressed selectively in IB4-binding C-fiber nociceptors hyperpolarizes their membrane potentials and limits spontaneous pain.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 114 citations in OpenAlex.
- Article
- Two pore domain THIK2 potassium channels regulate acute and chronic pain signaling.Pain reports · 2026Article
- Angiotensin II type 1 and type 2 receptors modulate TWIK1 channel expression and pain sensitivity in a rat model of neuropathic pain.Frontiers in pharmacology · 2026Article
- K2P channels as emerging therapeutic targets for pain: insights from functional studies and transcriptomic analyses.Frontiers in pharmacology · 2026Review
- Unraveling the Molecular Reason of Opposing Effects of α-Mangostin and Norfluoxetine on TREK-2 at the Same Binding Site.ChemMedChem · 2024Article
- TREK2 Lipid Binding Preferences Revealed by Native Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2024Article
- Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Atomistic mechanism of coupling between cytosolic sensor domain and selectivity filter in TREK K2P channels.Nature communications · 2024Article
- Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.Frontiers in molecular neuroscience · 2024Review
- Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.International journal of molecular sciences · 2023Review
- Multiple Effects of Echinochrome A on Selected Ion Channels Implicated in Skin Physiology.Marine drugs · 2023Article
- Spontaneous pain as a challenge of research and management in chronic pain.Medical review (2021) · 2022Review
- Development of Non-opioid Analgesics Targeting Two-pore Domain Potassium Channels.Current neuropharmacology · 2022Review
- Negative Influence by the Force: Mechanically Induced Hyperpolarization via KInternational journal of molecular sciences · 2021Review
- Two-Pore Domain Potassium Channel in Neurological Disorders.The Journal of membrane biology · 2021Review
- Emerging Role of PD-1 in the Central Nervous System and Brain Diseases.Neuroscience bulletin · 2021Review
- KCNK13 potassium channels in the ventral tegmental area of rats are important for excitation of ventral tegmental area neurons by ethanol.Alcoholism, clinical and experimental research · 2021Article
- A "Target Class" Screen to Identify Activators of Two-Pore Domain Potassium (K2P) Channels.SLAS discovery : advancing life sciences R & D · 2021Article
- Article
- Are TREK Channels Temperature Sensors?Frontiers in cellular neuroscience · 2021Review
5 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Ongoing/spontaneous pain behavior is associated with ongoing/spontaneous firing (SF) in adult DRG C-fiber nociceptors (Djouhri et al., 2006). Causes of this SF are not understood. We show here that conducting (sometimes called uninjured) C-nociceptors in neuropathic pain models with more hyperpolarized resting membrane potentials (Ems) have lower SF rates. Understanding the control of their Ems may therefore be important for limiting pathological pain. We report that TREK2, a leak K(+) channel, is selectively expressed in IB4 binding rat C-nociceptors. These IB4(+) C-neurons are ∼10 mV more hyperpolarized than IB4(-) C-neurons in vivo (Fang et al., 2006). TREK2 knockdown by siRNA in these neurons in culture depolarized them by ∼10 mV, suggesting that TREK2 is responsible for this ∼10 mV difference. In vivo, more hyperpolarized C-nociceptor Ems were associated with higher cytoplasmic edge-TREK2 expression (edge-TREK2). Edge-TREK2 decreased in C-neurons 7 d after axotomy, and their Ems depolarized by ∼10 mV. This again supports a contribution of TREK2 to their Ems. These relationships between (1) Em and TREK2, (2) SF rate and Em, and (3) spontaneous pain behavior and C-nociceptor SF rate suggested that TREK2 knockdown might increase spontaneous pain. After CFA-induced inflammation, spontaneous foot lifting (a measure of spontaneous pain) was (1) greater in rats with naturally lower TREK2 in ipsilateral small DRG neurons and (2) increased by siRNA-induced TREK2 knockdown in vivo. We conclude that TREK2 hyperpolarizes IB4 binding C-nociceptors and limits pathological spontaneous pain. Similar TREK2 distributions in small DRG neurons of several species suggest that these role(s) of TREK2 may be widespread.
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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.