Evidence mapPaperPMID 33402188Full record

ArticleJournal of neuroinflammation2021

P2X7R-mediated autophagic impairment contributes to central sensitization in a chronic migraine model with recurrent nitroglycerin stimulation in mice.

Li Jiang, Yixin Zhang, Feng Jing, Ting Long, Guangcheng Qin, Dunke Zhang, Lixue Chen, Jiying Zhou

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 4 pooled it
13.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 4 syntheses or guidelines pooled it, 112 citations in OpenAlex.

  1. Pooled it
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  5. Review
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  8. Non-neuronal targets for migraine therapy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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  20. Selective loss and transcriptional reprogramming of Nox4The journal of headache and pain · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Li JiangDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China.
Yixin ZhangDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China.
Feng JingDepartment of Neurology, Chongqing General Hospital, Chongqing, China.
Ting LongDepartment of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Guangcheng QinLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Dunke ZhangLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Lixue ChenLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Jiying ZhouDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China. zheadache@163.com.ORCID http://orcid.org/0000-0003-3923-4683
The Affiliated Yongchuan Hospital of Chongqing Medical University · CNAffiliated Hospital of Southwest Medical University · CNFirst People's Hospital of Chongqing · CN

Funding

National Natural Science Foundation of China 81671092National Natural Science Foundation of China 81971063
6 · The paper itself

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.

Indexed as

Disease Models, AnimalAnimalsAutophagyCentral Nervous System SensitizationChronic DiseaseMaleMiceMice, Inbred C57BLMigraine DisordersNitroglycerinReceptors, Purinergic P2X7Vasodilator AgentsNitroglycerinReceptors, Purinergic P2X7Vasodilator AgentsAutophagyCentral sensitizationChronic migraineInflammationMicrogliaP2X7R

Identifiers

PMID33402188
PMCPMC7786980
OpenAlexW3114587932

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.