Evidence mapPaperPMID 41398220Full record

ArticleThe journal of headache and pain2025

The P2Y13 receptor-mediated microglial morphological transformation through the p38MAPK signaling pathway contributes to central sensitization in a murine model of chronic migraine.

Yingjie Yang, Suya Sun, Pengtao Qin, Yalun Sun, Huijuan Li, Diandian Wang, Xin He, Zhaoming Ge, Zhenzhen Fan, Jiewen Zhang and 1 more

Abstract read
In one paragraph

Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
field-weighted citation impact
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

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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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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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

11 authors.

Yingjie Yang *Department of Neurology, Nanyang Central Hospital, Nanyang, Henan, 473000, China.
Suya Sun *Department of Nursing, Baoshan Branch, Huashan Hospital Affiliated to Fudan University, Jing'An, Shanghai, 201907, China.
Pengtao Qin *Department of Neurology, No 989 Hospital of Joint Logistic Support Force, Pingdingshan, Henan, 467000, China.
Yalun SunDepartment of Neurology, Henan Provincial People's Hospital, Henan University People's Hospital, Zhengzhou, Henan, 450003, China.
Huijuan LiDepartment of Neurology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
Diandian WangClinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Xin HeDepartment of Clinical Laboratory, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
Zhaoming GeDepartment of Neurology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, 730000, China.
Zhenzhen FanDepartment of Neurology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, 730000, China. fanzhzh21@163.com.
Jiewen ZhangDepartment of Neurology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China. zhangjiewen9900@126.com.
Songtang SunDepartment of Neurology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China. sstlucky@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCentral sensitization is a crucial pathophysiological mechanism of chronic migraine (CM), and neuroinflammation mediated by activated microglia contributes significantly to the development of central sensitization. The P2Y13 receptor (P2Y13R), belonging to the G protein-coupled receptor family, is expressed in microglia and actively participates in the intricate pathophysiological process underlying chronic neuropathic pain. However, the precise relationship between the P2Y13R and CM remains largely unclear.

methodsThe CM mouse model was established by repeatedly injecting nitroglycerin (NTG) intraperitoneally at intermittent intervals, and the pain threshold was assessed using von Frey fiber and hot plate tests. Specific interventions were conducted on the P2Y13R and p38 MAPK signaling pathways in the Trigeminal Nucleus Caudalis (TNC) of mice through stereotactic injection. Western blotting and immunofluorescence were employed to assess the expression and localization of P2Y13R, c-Fos, calcitonin gene-related peptide (CGRP), components of the p38 MAPK signaling pathway, and inflammatory factors.

resultsThe expression of P2Y13R was significantly upregulated upon NTG administration and exhibited a predominant distribution within the microglia in the TNC in mice with CM. Pharmacological inhibition of P2Y13R effectively reduced hyperalgesia in CM mice, lowered CGRP and c-fos levels, thereby improving central sensitization. Furthermore, inhibiting P2Y13R suppressed microglial activation and pro-inflammatory cytokine production. Additionally, activation of the p38MAPK pathway was observed in the TNC of CM mice, with P2Y13R inhibition significantly reducing p38MAPK pathway activity. Pharmacological inhibition of p38MAPK significantly ameliorates central sensitization in CM mice, while suppressing microglial activation and pro-inflammatory cytokine levels.

conclusionsThis research emphasizes the significance of P2Y13R in mediating central sensitization in CM mice through the p38MAPK pathway, thereby suggesting that targeting P2Y13R holds promise as a potential therapeutic strategy for effectively managing CM.

Indexed as

Central Nervous System SensitizationMAP Kinase Signaling SystemMicrogliaMigraine Disordersp38 Mitogen-Activated Protein KinasesReceptors, Purinergic P2AnimalsChronic DiseaseDisease Models, AnimalMaleMiceMice, Inbred C57BLNitroglycerinTrigeminal Caudal NucleusNitroglycerinp38 Mitogen-Activated Protein KinasesReceptors, Purinergic P2Central sensitizationMicrogliaP2Y13Rp38MAPKStereotactic injection

Identifiers

PMID41398220
PMCPMC12777325

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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.