ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Inhibition of M current in sensory neurons by exogenous proteases: a signaling pathway mediating inflammatory nociception.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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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
68 citing papers in PubMed, 116 citations in OpenAlex.
- Monoclonal antibody inhibition of PAR2 reduces phenotype severity and pain in murine inflammatory bowel disease.Pain reports · 2026Article
- Modulation of Nociceptive Ion Channels by Protease-Activated Receptor-2 in Inflammatory Pain: Molecular Mechanisms and Therapeutic Potential.International journal of molecular sciences · 2026Review
- Review
- TET1 Participates in Complete Freund's Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model.Neuroscience bulletin · 2024Article
- Selective KCNQ2/3 Potassium Channel Opener ICA-069673 Inhibits Excitability in Mouse Vagal Sensory Neurons.The Journal of pharmacology and experimental therapeutics · 2024Article
- KAmerican journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Inflammation differentially controls transport of depolarizing Nav versus hyperpolarizing Kv channels to drive rat nociceptor activity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Protease-activated receptors in health and disease.Physiological reviews · 2023Review
- KJournal of neurophysiology · 2021Article
- Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021Review
- Spinal PAR2 Activation Contributes to Hypersensitivity Induced by Peripheral Inflammation in Rats.International journal of molecular sciences · 2021Article
- Kv7 Channels and Excitability Disorders.Handbook of experimental pharmacology · 2021Article
- Neuropathic Injury-Induced Plasticity of GABAergic System in Peripheral Sensory Ganglia.Frontiers in pharmacology · 2021Article
- Physiology and Therapeutic Potential of SK, H, and M Medium AfterHyperPolarization Ion Channels.Frontiers in molecular neuroscience · 2021Review
- Pharmacological Activation of Neuronal Voltage-Gated Kv7/KCNQ/M-Channels for Potential Therapy of Epilepsy and Pain.Handbook of experimental pharmacology · 2021Article
- Transcriptomic sex differences in sensory neuronal populations of mice.Scientific reports · 2020Article
- Role of TRP channels in GAmerican journal of physiology. Lung cellular and molecular physiology · 2020Article
- KFrontiers in cellular neuroscience · 2020Review
- Inhibition of M/KFrontiers in molecular neuroscience · 2020Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Inflammatory pain is thought to be mediated in part through the action of inflammatory mediators on membrane receptors of peripheral nerve terminals, however, the downstream signaling events which lead to pain are poorly understood. In this study we investigated the nociceptive pathways induced by activation of protease-activated receptor 2 (PAR-2) in damage-sensing (nociceptive) neurons from rat dorsal root ganglion (DRG). We found that activation of PAR-2 in these cells strongly inhibited M-type potassium currents (conducted by Kv7 potassium channels). Such inhibition caused depolarization of the neuronal resting membrane potential leading, ultimately, to nociception. Consistent with this mechanism, injection of the specific M channel blocker XE991 into rat paw induced nociception in a concentration-dependent manner. Injection of a PAR-2 agonist peptide also induced nociception but coinjection of XE991 and the PAR-2 agonist did not result in summation of nociception, suggesting that the action of both agents may share a similar mechanism. We also studied the signaling pathway of M current inhibition by PAR-2 using patch-clamp and fluorescence imaging of DRG neurons. These experiments revealed that the PAR-2 effect was mediated by phospholipase C (PLC). Further experiments demonstrated that M current inhibition required concurrent rises in cytosolic Ca(2+) concentration and depletion of membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)). We propose that PLC- and Ca(2+)/PIP(2)-mediated inhibition of M current in sensory neurons may represent one of the general mechanisms underlying pain produced by inflammatory mediators, and may therefore open up a new therapeutic window for treatment of this major clinical problem.
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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.