ArticleMolecular pain
Synergistic activation of ERK1/2 between A-fiber neurons and glial cells in the DRG contributes to pain hypersensitivity after tissue injury.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.Current neuropharmacology · 2025Review
- Involvement of sphingosine-1-phosphate receptor 1 in pain insensitivity in a BTBR mouse model of autism spectrum disorder.BMC medicine · 2024Article
- Plp1-expresssing perineuronal DRG cells facilitate colonic and somatic chronic mechanical pain involving Piezo2 upregulation in DRG neurons.Cell reports · 2024Article
- MERTK in the rat trigeminal system: a potential novel target for cluster headache?The journal of headache and pain · 2024Article
- Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.Neurochemical research · 2023Article
- Activation of Intra-nodose Ganglion P2X7 Receptors Elicit Increases in Neuronal Activity.Cellular and molecular neurobiology · 2023Article
- SARS-CoV-2 airway infection results in the development of somatosensory abnormalities in a hamster model.Science signaling · 2023Article
- Single-cell transcriptomic profile of satellite glial cells in trigeminal ganglion.Frontiers in molecular neuroscience · 2023Article
- SARS-CoV-2 Airway Infection Results in Time-dependent Sensory Abnormalities in a Hamster Model.bioRxiv : the preprint server for biology · 2022Article
- Review
- Advancing the Understanding of Acupoint Sensitization and Plasticity Through Cutaneous C-Nociceptors.Frontiers in neuroscience · 2022Review
- Heterogeneity and Potency of Peripheral Glial Cells in Embryonic Development and Adults.Frontiers in molecular neuroscience · 2022Review
- Metabolic Transporters in the Peripheral Nerve-What, Where, and Why?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Recent Advances in Pain Management: Relevant Protein Kinases and Their Inhibitors.Molecules (Basel, Switzerland) · 2021Review
- Purinergic Signaling in Endometriosis-Associated Pain.International journal of molecular sciences · 2020Review
- Emerging importance of satellite glia in nervous system function and dysfunction.Nature reviews. Neuroscience · 2020Review
- A novel primary culture method for high-purity satellite glial cells derived from rat dorsal root ganglion.Neural regeneration research · 2019Article
- Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain.Journal of anesthesia · 2019Review
- Rapid cleavage of IL-1β in DRG neurons produces tissue injury-induced pain hypersensitivity.Molecular painArticle
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background Intense nociceptive signaling arising from ongoing injury activates primary afferent nociceptive systems to generate peripheral sensitization. ERK1/2 phosphorylation in dorsal root ganglion can be used to visualize intracellular signal activity immediately after noxious stimulation. The aim of this study was to investigate spatiotemporal characteristics of ERK1/2 phosphorylation against tissue injury in the primary afferent neurons. Methods Plantar incisions were made in the hind paws of Sprague-Dawley rats (n =150). Levobupivacaine was injected into the plantar aspect of the paws and ankles, Mitogen-activated protein kinase kinase (MEK) inhibitor was injected into the paw, and carbenoxolone, dual inhibitor of the gap junction and pannexin channel, was intraperitoneally injected. Pain hypersensitivity was investigated by a behavioral study, while phosphorylated ERK1/2 was detected in dorsal root ganglion and hind paw using immunohistochemistry and Western blot. Results Phosphorylated ERK1/2 was induced in dorsal root ganglion (26.8 ± 2.9% at baseline, 65.6 ± 3.6% at 2 min, and 26.3 ± 3.4% at 2 h) after the incision. NF-200 positive A-fiber neurons and satellite glial cells were positive for phosphorylated ERK1/2. Injury-induced pain hypersensitivity was abolished by MEK inhibitor. Levobupivacaine treatment inhibited phosphorylated ERK1/2 induction, carbenoxolone treatment inhibited glial phosphorylated ERK1/2 at 2 min after the injury, and carbenoxolone inhibited pain hypersensitivity and neuronal phosphorylated ERK1/2 at 1 h after the injury. Conclusion ERK1/2 phosphorylation in A-fiber neurons and satellite glial cells immediately after injury contributes to the generation of pain hypersensitivity. Signal communication between neurons and satellite glial cells expands the duration of neuronal ERK1/2 phosphorylation and pain hypersensitivity at 1 h after tissue injury.
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