ArticleJournal of neuroinflammation2021
P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 4 of them syntheses that pooled it.
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Who cites it
57 citing papers in PubMed, 4 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- The mechanism of different microglial receptors mediating central inflammation in chronic migraine: a meta-analysis.The journal of headache and pain · 2026Pooled it
- Mapping the immune and epigenetic landscape of medication-overuse headache (MOH): a systematic review.Frontiers in immunology · 2026Pooled it
- Cross-trait analyses identify shared genetics between migraine, headache, and glycemic traits, and a causal relationship with fasting proinsulin.Human genetics · 2023Pooled it
- A systematic literature review on the role of glial cells in the pathomechanisms of migraine.Frontiers in molecular neuroscience · 2023Pooled it
- P2X7 Receptor as a Therapeutic Target for Neuropathic Pain: From Mechanisms to Translational Strategies.Current pain and headache reports · 2026Review
- NIR-II Imaging-Guided Photothermal Activation of a TRPV4-Targeted Nanoplatform Delivering Cycloastragenol to Promote Microglia Reprogramming and α-Synuclein Clearance in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Polydatin Relieves Airway Remodeling by Inhibiting P2X7R-NLRP3-Mediated Excessive Autophagy in Asthma.Immunity, inflammation and disease · 2026Article
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- TREM2 contributes to central sensitization through PI3K/Akt/mTOR-mediated autophagic dysfunction in a rat model of vestibular migraine.The journal of headache and pain · 2026Article
- Neuroinflammatory control of metabolism in huntington's disease: central role of P2 × 7 receptor mediated redox lipid/epigenetic crosstalk.Inflammopharmacology · 2026Review
- Extracellular Vesicles in Migraine: Biomarkers and Therapeutics.Molecular neurobiology · 2026Review
- Alleviation of nitroglycerin-induced migraine in rats: inhibition of central sensitization by optimizing Qinggan Jieyu decoction regulation of purinergic receptor P2X ligand-gated ion channel 7 and autophagy.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- Oxidative Stress and Mitophagy in Rats With Nitroglycerin/Inflammatory Soup-Induced Migraine: A Comparative Study.Pain research & management · 2026Article
- TGM2-P2RX7 loop promotes gemcitabine resistance in pancreatic cancer by modulating glutamine metabolism and mitophagy.Cell death discovery · 2025Article
- From trigeminal ganglion to cortex: ATG7 emerges as a key integrator of migraine pathways via multi-omics profiling.The journal of headache and pain · 2025Article
- The P2Y13 receptor-mediated microglial morphological transformation through the p38MAPK signaling pathway contributes to central sensitization in a murine model of chronic migraine.The journal of headache and pain · 2025Article
- Changes in oxidative stress and inflammation biomarkers in the pathogenesis of migraine: possible relationships with lipid metabolism.BMC neurology · 2025Article
- P2RX7 Dynamics in CNS Disorders: Molecular Insights and Therapeutic Perspectives.Molecular neurobiology · 2025Review
- Selective loss and transcriptional reprogramming of Nox4The journal of headache and pain · 2025Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCentral sensitization is an important pathophysiological mechanism of chronic migraine (CM). According to our previous studies, microglial activation and subsequent inflammation in the trigeminal nucleus caudalis (TNC) contribute to the central sensitization. The P2X7 receptor (P2X7R) is a purinergic receptor expressed in microglia and participates in central sensitization in chronic pain, but its role in CM is unclear. Numerous studies have shown that P2X7R regulates the level of autophagy and that autophagy affects the microglial activation and inflammation. Recently, autophagy has been shown to be involved in neuropathic pain, but there is no information about autophagy in CM. Therefore, the current study investigated the role of P2X7R in CM and its underlying mechanism, focusing on autophagy regulation.
methodsThe CM model was established by repeated intraperitoneal injection of nitroglycerin (NTG) in mice. A Von Frey filament and radiant heat were used to assess the mechanical and thermal hypersensitivity. Western blotting and immunofluorescence assays were performed to detect the expression of P2X7R, autophagy-related proteins, and the cellular localization of P2X7R. To determine the role of P2X7R and autophagy in CM, we detected the effects of the autophagy inducer, rapamycin (RAPA) and P2X7R antagonist, Brilliant Blue G (BBG), on pain behavior and the expression of calcitonin gene-related peptide (CGRP) and c-fos. In addition, the effect of RAPA and BBG on microglial activation and subsequent inflammation were investigated.
resultsThe expression of P2X7R was increased and was mainly colocalized with microglia in the TNC following recurrent NTG administration. The autophagic flux was blocked in CM, which was characterized by upregulated LC3-II, and accumulated autophagy substrate protein, p62. RAPA significantly improved the basal rather than acute hyperalgesia. BBG alleviated both basal and acute hyperalgesia. BBG activated the level of autophagic flux. RAPA and BBG inhibited the activation of microglia, limited the inflammatory response, and reduced the expression of CGRP and c-fos.
conclusionsOur results demonstrate the dysfunction of the autophagic process in CM. Activated autophagy may have a preventive effect on migraine chronification. P2X7R contributes to central sensitization through mediating autophagy regulation and might become a potential target for CM.
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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 Socratic graph.