ArticleThe journal of pain2015
Peripheral group I metabotropic glutamate receptor activation leads to muscle mechanical hyperalgesia through TRPV1 phosphorylation in the rat.
Article in The journal of pain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- TRP Channels in Excitotoxicity.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.Current neuropharmacology · 2024Review
- Selective activation of AKAP150/TRPV1 in ventrolateral periaqueductal gray GABAergic neurons facilitates conditioned place aversion in male mice.Communications biology · 2023Article
- Peripheral role of glutamate in orofacial pain.Frontiers in neuroscience · 2022Review
- Dysregulation of the peripheral glutamatergic system: A key player in migraine pathogenesis?Cephalalgia : an international journal of headache · 2021Review
- Neural Pathways of Craniofacial Muscle Pain: Implications for Novel Treatments.Journal of dental research · 2020Review
- Phosphorylation of TRPV1 S801 Contributes to Modality-Specific Hyperalgesia in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- TRPV1 Channel Contributes to the Behavioral Hypersensitivity in a Rat Model of Complex Regional Pain Syndrome Type 1.Frontiers in pharmacology · 2019Article
- TRPV1 channel contributes to remifentanil-induced postoperative hyperalgesia via regulation of NMDA receptor trafficking in dorsal root ganglion.Journal of pain research · 2019Article
- Antinociceptive Activity of Petroleum Ether Fraction ofBioMed research international · 2019Article
- KChIP3 N-Terminal 31-50 Fragment Mediates Its Association with TRPV1 and Alleviates Inflammatory Hyperalgesia in Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Emerging Trends in Pain Modulation by Metabotropic Glutamate Receptors.Frontiers in molecular neuroscience · 2018Review
- H89 dihydrochloride hydrate and calphostin C lower the body temperature through TRPV1.Molecular medicine reports · 2018Article
- Parathyroid Hormone-Related Peptide Elicits Peripheral TRPV1-dependent Mechanical Hypersensitivity.Frontiers in cellular neuroscience · 2018Article
- A-Kinase Anchoring Protein 79/150 Scaffolds Transient Receptor Potential A 1 Phosphorylation and Sensitization by Metabotropic Glutamate Receptor Activation.Scientific reports · 2017Article
- Activation of TRPM2 and TRPV1 Channels in Dorsal Root Ganglion by NADPH Oxidase and Protein Kinase C Molecular Pathways: a Patch Clamp Study.Journal of molecular neuroscience : MN · 2017Article
- Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways.Current neuropharmacology · 2017Article
- Transcriptome analysis of trigeminal ganglia following masseter muscle inflammation in rats.Molecular pain · 2016Article
- Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury.Molecular pain · 2016Article
- The role of TRPA1 in muscle pain and mechanical hypersensitivity under inflammatory conditions in rats.Neuroscience · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledElevated glutamate levels within injured muscle play important roles in muscle pain and hyperalgesia. In this study, we hypothesized that protein kinase C (PKC)-dependent TRPV1 phosphorylation contributes to the muscle mechanical hyperalgesia following activation of Group I metabotropic glutamate receptors (mGlu1/5). Mechanical hyperalgesia induced by (R,S)-3,5-dihydroxyphenylglycine (DHPG), an mGlu1/5 agonist, in the masseter muscle was attenuated by AMG9810, a specific TRPV1 antagonist. AMG9810 also suppressed mechanical hyperalgesia evoked by pharmacologic activation of PKC. DHPG-induced mechanical hyperalgesia was suppressed by pretreatment with a decoy peptide that disrupted interactions between TRPV1 and A-kinase-anchoring protein (AKAP), which facilitates phosphorylation of TRPV1. In dissociated trigeminal ganglia, DHPG upregulated serine phosphorylation of TRPV1 (S800), during which DHPG-induced mechanical hyperalgesia was prominent. The TRPV1 phosphorylation at S800 was suppressed by a PKC inhibitor. Electrophysiologic measurements in trigeminal ganglion neurons demonstrated that TRPV1 sensitivity was enhanced by pretreatment with DHPG, and this was prevented by a PKC inhibitor, but not by a protein kinase A inhibitor. These results suggest that mGlu1/5 activation in masseter afferents invokes phosphorylation of TRPV1 serine residues including S800, and that phosphorylation-induced sensitization of TRPV1 is involved in masseter mechanical hyperalgesia. These data support a role of TRPV1 as an integrator of glutamate receptor signaling in muscle nociceptors. PERSPECTIVE: This article demonstrates that activation of mGlu1/5 leads to phosphorylation of a specific TRPV1 residue via PKC and AKAP150 in trigeminal sensory neurons and that functional interactions between glutamate receptors and TRPV1 mediate mechanical hyperalgesia in the muscle tissue.
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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.