ArticlePain2012
Reactive oxygen species (ROS) modulate AMPA receptor phosphorylation and cell-surface localization in concert with pain-related behavior.
Article in Pain, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- AT1R in Central Nervous System Disorders: Unveiling Novel Mechanisms and Therapeutic Avenues for Addiction.Addiction biology · 2026Review
- LARGE protein drives activity-induced homeostatic resetting.Science advances · 2025Article
- Decoding the mechanism of proanthocyanidins in central analgesia: redox regulation and KCNK3 blockade.Experimental & molecular medicine · 2025Article
- Decoding pain chronification: mechanisms of the acute-to-chronic transition.Frontiers in molecular neuroscience · 2025Review
- Dopamine D2 Receptor Activation Blocks GluA2/ROS Positive Feedback Loop to Alienate Chronic-Migraine-Associated Pain Sensitization.Antioxidants (Basel, Switzerland) · 2024Article
- Activity-dependent mitochondrial ROS signaling regulates recruitment of glutamate receptors to synapses.eLife · 2024Article
- Heat Shock Protein 22 Attenuates Nerve Injury-induced Neuropathic Pain Via Improving Mitochondrial Biogenesis and Reducing Oxidative Stress Mediated By Spinal AMPK/PGC-1α Pathway in Male Rats.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Spinal antinociceptive effect of the PnTx4(5-5) peptide is possibly mediated by the NMDA autoreceptors.The journal of venomous animals and toxins including tropical diseases · 2024Article
- SIRT1-regulated ROS generation activates NMDAR2B phosphorylation to promote central sensitization and allodynia in a male chronic migraine rat model.Frontiers in molecular neuroscience · 2024Article
- Ferroptosis: a new regulatory mechanism in neuropathic pain.Frontiers in aging neuroscience · 2023Review
- Intraganglionic reactive oxygen species mediate inflammatory pain and hyperalgesia through TRPA1 in the rat.Frontiers in pain research (Lausanne, Switzerland) · 2023Article
- The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration.Biomedicines · 2022Review
- NADPH Oxidases in Pain Processing.Antioxidants (Basel, Switzerland) · 2022Review
- Transgenic Mouse Overexpressing Spermine Oxidase in Cerebrocortical Neurons: Astrocyte Dysfunction and Susceptibility to Epileptic Seizures.Biomolecules · 2022Review
- The Roles of Superoxide on At-Level Spinal Cord Injury Pain in Rats.International journal of molecular sciences · 2021Article
- Nitric Oxide Signaling Strengthens Inhibitory Synapses of Cerebellar Molecular Layer Interneurons through a GABARAP-Dependent Mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Neuronal Cells Rearrangement During Aging and Neurodegenerative Disease: Metabolism, Oxidative Stress and Organelles Dynamic.Frontiers in molecular neuroscience · 2019Article
- Article
- LARGE, an intellectual disability-associated protein, regulates AMPA-type glutamate receptor trafficking and memory.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain.Redox biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Sensitization of dorsal horn neurons (DHNs) in the spinal cord is dependent on pain-related synaptic plasticity and causes persistent pain. The DHN sensitization is mediated by a signal transduction pathway initiated by the activation of N-methyl-d-aspartate receptors (NMDA-Rs). Recent studies have shown that elevated levels of reactive oxygen species (ROS) and phosphorylation-dependent trafficking of GluA2 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPA-Rs) are a part of the signaling pathway for DHN sensitization. However, the relationship between ROS and AMPA-R phosphorylation and trafficking is not known. Thus, this study investigated the effects of ROS scavengers on the phosphorylation and cell-surface localization of GluA1 and GluA2. Intrathecal NMDA- and intradermal capsaicin-induced hyperalgesic mice were used for this study since both pain models share the NMDA-R activation-dependent DHN sensitization in the spinal cord. Our behavioral, biochemical, and immunohistochemical analyses demonstrated that: 1) NMDA-R activation in vivo increased the phosphorylation of AMPA-Rs at GluA1 (S818, S831, and S845) and GluA2 (S880) subunits; 2) NMDA-R activation in vivo increased cell-surface localization of GluA1 but decreased that of GluA2; and 3) reduction of ROS levels by ROS scavengers PBN (N-tert-butyl-α-phenylnitrone) or TEMPOL (4-hydroxy-2, 2, 6, 6-tetramethylpiperidin-1-oxyl) reversed these changes in AMPA-Rs, as well as pain-related behavior. Given that AMPA-R trafficking to the cell surface and synapse is regulated by NMDA-R activation-dependent phosphorylation of GluA1 and GluA2, our study suggests that the ROS-dependent changes in the phosphorylation and cell-surface localization of AMPA-Rs are necessary for DHN sensitization and thus, pain-related behavior. We further suggest that ROS reduction will ameliorate these molecular changes and pain.
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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.