ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Metabotropic glutamate receptor 5 modulates nociceptive plasticity via extracellular signal-regulated kinase-Kv4.2 signaling in spinal cord dorsal horn neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 110 citations in OpenAlex.
- A type-5 metabotropic glutamate receptor-perineuronal net axis shapes the function of cortical GABAergic interneurons in chronic pain.Journal of anesthesia, analgesia and critical care · 2025Review
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- Involvement of Mrgprd-expressing nociceptors-recruited spinal mechanisms in nerve injury-induced mechanical allodynia.iScience · 2023Article
- A prototype closed-loop brain-machine interface for the study and treatment of pain.Nature biomedical engineering · 2023Article
- A compendium of validated pain genes.WIREs mechanisms of disease · 2022Review
- Review
- Identification of Kv4.2 protein complex and modifications by tandem affinity purification-mass spectrometry in primary neurons.Frontiers in cellular neuroscience · 2022Article
- Blocking the Spinal Fbxo3/CARM1/KNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy.American journal of human genetics · 2021Article
- Systems and Circuits Linking Chronic Pain and Circadian Rhythms.Frontiers in neuroscience · 2021Review
- Single-Cell RNA Analysis of Type I Spiral Ganglion Neurons Reveals aFrontiers in molecular neuroscience · 2020Article
- SIRT1 Activation Attenuates Bone Cancer Pain by Inhibiting mGluR1/5.Cellular and molecular neurobiology · 2019Article
- mGluR5/ERK signaling regulated the phosphorylation and function of glycine receptor α1ins subunit in spinal dorsal horn of mice.PLoS biology · 2019Article
- Neuritin promotes neurite and spine growth in rat cerebellar granule cells via L-type calcium channel-mediated calcium influx.Journal of neurochemistry · 2018Article
- Article
- Emerging Trends in Pain Modulation by Metabotropic Glutamate Receptors.Frontiers in molecular neuroscience · 2018Review
- The human transient receptor potential vanilloid 3 channel is sensitized via the ERK pathway.The Journal of biological chemistry · 2017Article
- Review
- BDNF Contributes to Spinal Long-Term Potentiation and Mechanical Hypersensitivity Via Fyn-Mediated Phosphorylation of NMDA Receptor GluN2B Subunit at Tyrosine 1472 in Rats Following Spinal Nerve Ligation.Neurochemical research · 2017Article
- Optical control of paineLife · 2017Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Metabotropic glutamate receptors (mGluRs) play important roles in the modulation of nociception. The group I mGluRs (mGlu1 and mGlu5) modulate nociceptive plasticity via activation of extracellular signal-regulated kinase (ERK) signaling. We reported recently that the K+ channel Kv4.2 subunit underlies A-type K+ currents in the spinal cord dorsal horn and is modulated by the ERK signaling pathway. Kv4.2-mediated A-type currents are important determinants of dorsal horn neuronal excitability and central sensitization that underlies hypersensitivity after tissue injury. In the present study, we demonstrate that ERK-mediated phosphorylation of Kv4.2 is downstream of mGlu5 activation in spinal cord dorsal horn neurons. Activation of group I mGluRs inhibited Kv4.2-mediated A-type K+ currents and increased neuronal excitability in dorsal horn neurons. These effects were mediated by activation of mGlu5, but not mGlu1, and were dependent on ERK activation. Analysis of Kv4.2 phosphorylation site mutants clearly identified S616 as the residue responsible for mGlu5-ERK-dependent modulation of A-type currents and excitability. Furthermore, nociceptive behavior induced by activation of spinal group I mGluRs was impaired in Kv4.2 knock-out mice, demonstrating that, in vivo, modulation of Kv4.2 is downstream of mGlu5 activation. Altogether, our results indicate that activation of mGlu5 leads to ERK-mediated phosphorylation and modulation of Kv4.2-containing potassium channels in dorsal horn neurons. This modulation may contribute to nociceptive plasticity and central sensitization associated with chronic inflammatory pain conditions.
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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.