ArticleJournal of neuroinflammation2018
Microglia P2X4 receptor contributes to central sensitization following recurrent nitroglycerin stimulation.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 2 of them syntheses that pooled it.
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Who cites it
54 citing papers in PubMed, 2 syntheses or guidelines pooled it, 114 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
- A systematic literature review on the role of glial cells in the pathomechanisms of migraine.Frontiers in molecular neuroscience · 2023Pooled it
- The Role of Vitamin D in Neuropathic Pain: Biological Mechanisms and Clinical Relevance.International journal of molecular sciences · 2026Review
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Low-Intensity Pulsed Ultrasound Alleviation of LPS-Induced Depression-Like Behavior via Microglial P2X4R Inhibition and BDNF/TrkB Pathway Activation.CNS neuroscience & therapeutics · 2026Article
- Targeting glial-orchestrated neuroinflammation in migraine pathophysiology.The journal of headache and pain · 2026Review
- Neuroinflammatory and Redox Responses in a Rat Model of NTG-Induced Migraine.International journal of molecular sciences · 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
- Analgesic Mechanism of Emodin in Neuropathic Pain Through Inhibiting P2X4 Purinoceptor Signaling.Molecular neurobiology · 2025Article
- The Proteomic Analysis of Chronic Migraine Exosomes Reveals Disease Patterns and Potential Biomarkers.Molecular neurobiology · 2025Article
- Metformin attenuates central sensitization by regulating neuroinflammation through the TREM2-SYK signaling pathway in a mouse model of chronic migraine.Journal of neuroinflammation · 2024Article
- Neuroimmune interactions in the development and chronification of migraine headache.Trends in neurosciences · 2024Review
- The role of kynurenines in migraine-related neuroimmune pathways.The journal of headache and pain · 2024Review
- TLR2 Mediates Microglial Activation and Contributes to Central Sensitization in a Recurrent Nitroglycerin-induced Chronic Migraine Model.Molecular neurobiology · 2024Article
- Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice.The journal of headache and pain · 2024Article
- Elucidating the mechanisms underlying astrocyte-microglia crosstalk in hippocampal neuroinflammation induced by acute diquat exposure.Environmental science and pollution research international · 2024Article
- Modulation of Microglial Function by ATP-Gated P2X7 Receptors: Studies in Rat, Mice and Human.Cells · 2024Review
- Microglia TREM1-mediated neuroinflammation contributes to central sensitization via the NF-κB pathway in a chronic migraine model.The journal of headache and pain · 2024Article
- Advances in understanding migraine pathophysiology: a bench to bedside review of research insights and therapeutics.Frontiers in molecular neuroscience · 2024Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe mechanism underlying migraine chronification remains unclear. Central sensitization may account for this progression. The microglia P2X4 receptor (P2X4R) plays a pivotal role in the central sensitization of inflammatory and neuropathic pain, but there is no information about P2X4R in migraine. Therefore, the aim of this study was to identify the precise role of microglia P2X4R in chronic migraine (CM).
methodsWe used an animal model with recurrent intermittent administration of nitroglycerin (NTG), which closely mimics CM. NTG-induced basal and acute mechanical hypersensitivity were evaluated using the von Frey filament test. Then, we detected Iba1 immunoreactivity (Iba1-IR) and P2X4R expression in the trigeminal nucleus caudalis (TNC). To understand the effect of microglia and P2X4R on central sensitization of CM, we examined whether minocycline, an inhibitor of microglia activation, and 5-BDBD, a P2X4R antagonist, altered NTG-induced mechanical hyperalgesia. In addition, we also evaluated the effect of 5-BDBD on c-Fos and calcitonin gene-related peptide (CGRP) expression within the TNC.
resultsChronic intermittent administration of NTG resulted in acute and chronic basal mechanical hyperalgesia, accompanied with microglia activation and upregulation of P2X4R expression. Minocycline significantly decreased basal pain hypersensitivity but did not alter acute NTG-induced hyperalgesia. Minocycline also reduced microglia activation. 5-BDBD completely blocked the basal and acute hyperalgesia induced by NTG. This effect was associated with a significant inhibition of the NTG-induced increase in c-Fos protein and CGRP release in the TNC.
conclusionsOur results indicate that blocking microglia activation may have an effect on the prevention of migraine chronification. Moreover, we speculate that the P2X4R may be implicated in the microglia-neuronal signal in the TNC, which contributes to the central sensitization of CM.
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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.