ArticleThe journal of headache and pain2022
Dopamine receptor D2 regulates GLUA1-containing AMPA receptor trafficking and central sensitization through the PI3K signaling pathway in a male rat model of chronic migraine.
Article in The journal of headache and pain, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Genetic Basis of the Negative Response to the Use of Triptans for the Treatment of Migraine-A Systematic Review and Meta-Analysis.Brain and behavior · 2025Pooled it
- Trial
- Targeting the microbiome in pediatric migraine: gastrointestinal manifestations and the therapeutic role ofGut microbes · 2026Article
- Therapeutic potential of CMPP, a novel maleimide derivative, in a reserpine-induced mouse model of pain-depression dyad.Biochemistry and biophysics reports · 2026Article
- Dopaminergic Dysregulation in Migraine: From Hypothalamic A11 Dysfunction to a Systemic Biobehavioral Phenotype.International journal of molecular sciences · 2026Review
- SP1 recruits TET1 to mediate Kif1a demethylation and synaptic remodeling in a mouse model of chronic migraine.The journal of headache and pain · 2026Article
- Downregulation of neuronal DRD2 drives microglia synaptic pruning and results in cognitive deficits by promoting CCL2 release in a rat model of chronic migraine.The journal of headache and pain · 2026Article
- Long-term survival in glioblastoma patients treated with dopamine agonists: A report of two cases and implications for drug repurposing.Surgical neurology international · 2026Article
- Dopamine and prolactin in migraine: Mechanisms and potential therapeutic targets.Journal of neuroendocrinology · 2025Review
- Mechanistic intersections between migraine and major depressive disorder.The journal of headache and pain · 2025Review
- Regulating AMPA Receptors with Isoxazole-4-Carboxamide Derivatives: An Electrophysiological Study.Journal of xenobiotics · 2025Article
- The Proteomic Analysis of Chronic Migraine Exosomes Reveals Disease Patterns and Potential Biomarkers.Molecular neurobiology · 2025Article
- The Potential Role of Glutamate Receptors and their Antagonists or Modulators in Migraine Therapy.Current neuropharmacology · 2025Review
- Mechanisms of glutamate receptors hypofunction dependent synaptic transmission impairment in the hippocampus of schizophrenia susceptibility gene Opcml-deficient mouse model.Molecular brain · 2024Article
- Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve.Chinese journal of integrative medicine · 2024Article
- Dopamine D2 Receptor Activation Blocks GluA2/ROS Positive Feedback Loop to Alienate Chronic-Migraine-Associated Pain Sensitization.Antioxidants (Basel, Switzerland) · 2024Article
- Upregulation of Spinal MDGA1 in Rats After Nerve Injury Alters Interactions Between Neuroligin-2 and Postsynaptic Scaffolding Proteins and Increases GluR1 Subunit Surface Delivery in the Spinal Cord Dorsal Horn.Neurochemical research · 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
- A novel opioid/pramipexole combination treatment for the management of acute pain: a pilot study.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Molecular Mechanisms of AMPA Receptor Trafficking in the Nervous System.International journal of molecular sciences · 2023Review
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7 authors at 2 institutions in 1 country.
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Abstract
backgroundThe pathogenesis of chronic migraine remains unresolved. Recent studies have affirmed the contribution of GLUA1-containing AMPA receptors to chronic migraine. The dopamine D2 receptor, a member of G protein-coupled receptor superfamily, has been proven to have an analgesic effect on pathological headaches. The present work investigated the exact role of the dopamine D2 receptor in chronic migraine and its effect on GLUA1-containing AMPA receptor trafficking.
methodsA chronic migraine model was established by repeated inflammatory soup stimulation. Mechanical, periorbital, and thermal pain thresholds were assessed by the application of von Frey filaments and radiant heat. The mRNA and protein expression levels of the dopamine D2 receptor were analyzed by qRT‒PCR and western blotting. Colocalization of the dopamine D2 receptor and the GLUA1-containing AMPAR was observed by immunofluorescence. A dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride), a PI3K inhibitor (LY294002), a PI3K pathway agonist (740YP), and a GLUA1-containing AMPAR antagonist (NASPM) were administered to confirm the effects of the dopamine D2 receptor, the PI3K pathway and GULA1 on central sensitization and the GLUA1-containing AMPAR trafficking. Transmission electron microscopy and Golgi-Cox staining were applied to assess the impact of the dopamine D2 receptor and PI3K pathway on synaptic morphology. Fluo-4-AM was used to clarify the role of the dopamine D2 receptor and PI3K signaling on neuronal calcium influx. The Src family kinase (SFK) inhibitor PP2 was used to explore the effect of Src kinase on GLUA1-containing AMPAR trafficking and the PI3K signaling pathway.
resultsInflammatory soup stimulation significantly reduced pain thresholds in rats, accompanied by an increase in PI3K-P110β subunit expression, loss of dopamine receptor D2 expression, and enhanced GLUA1-containing AMPA receptor trafficking in the trigeminal nucleus caudalis (TNC). The dopamine D2 receptor colocalized with the GLUA1-containing AMPA receptor in the TNC; quinpirole, LY294002, and NASPM alleviated pain hypersensitivity and reduced GLUA1-containing AMPA receptor trafficking in chronic migraine rats. Sulpiride aggravated pain hypersensitivity and enhanced GLUA1 trafficking in CM rats. Importantly, the anti-injury and central sensitization-mitigating effects of quinpirole were reversed by 740YP. Both quinpirole and LY294002 inhibited calcium influx to neurons and modulated the synaptic morphology in the TNC. Additional results suggested that DRD2 may regulate PI3K signaling through Src family kinases.
conclusionModulation of GLUA1-containing AMPA receptor trafficking and central sensitization by the dopamine D2 receptor via the PI3K signaling pathway may contribute to the pathogenesis of chronic migraine in rats, and the dopamine D2 receptor could be a valuable candidate for chronic migraine treatment.
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