Evidence map›Paper›PMID 35144528›Full record

ArticleThe journal of headache and pain2022

Sphingosine-1 phosphate receptor 1 contributes to central sensitization in recurrent nitroglycerin-induced chronic migraine model.

Qi Pan, Yunfeng Wang, Ruimin Tian, Qianwen Wen, Guangcheng Qin, Dunke Zhang, Lixue Chen, Yixin Zhang, Jiying Zhou

Open access · goldAbstract read
In one paragraph

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 23 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 3 pooled it
2.6field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 3 syntheses or guidelines pooled it, 26 citations in OpenAlex.

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  9. Selective loss and transcriptional reprogramming of Nox4The journal of headache and pain · 2025
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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

9 authors at 2 institutions in 1 country.

Qi Pan *Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China.
Yunfeng Wang *Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China.
Ruimin TianDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China.
Qianwen WenLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 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.
Yixin ZhangDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1st You Yi Road, Yuzhong District, Chongqing, 400016, China. zhangyx_cq@163.com.
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 · CNNorth Sichuan Medical University · CN

Funding

National Natural Science Foundation of China 81971063National Natural Science Foundation of China 82101296the Cultivation Fund of The First Affiliated Hospital of Chongqing Medical University ZYRC2020-01
6 · The paper itself

Abstract

backgroundCentral sensitization is an important pathophysiological mechanism of chronic migraine (CM), and microglia activation in trigeminocervical complex (TCC) contributes to the development of central sensitization. Emerging evidence implicates that blocking sphingosine-1-phosphate receptor 1 (S1PR1) can relieve the development of chronic pain and inhibit the activation of microglia. However, it is unclear whether S1PR1 is involved in the central sensitization of CM. Therefore, the purpose of this study is to explore the role of S1PR1 and its downstream signal transducers and activators of transcription 3 (STAT3) signaling pathway in the CM, mainly in inflammation.

methodsChronic intermittent intraperitoneal injection of nitroglycerin (NTG) established a mouse model of CM. First, we observed the changes and subcellular localization of S1PR1 in the trigeminocervical complex (TCC). Then, W146, a S1PR1 antagonist; SEW2871, a S1PR1 agonist; AG490, a STAT3 inhibitor were applied by intraperitoneal injection to investigate the related molecular mechanism. The changes in the number of microglia and the expression of calcitonin gene-related peptide (CGRP) and c-fos in the TCC site were explored by immunofluorescence. In addition, we studied the effect of S1PR1 inhibitors on STAT3 in lipopolysaccharide-treated BV-2 microglia.

resultsOur results showed that the expression of S1PR1 was increased after NTG injection and S1PR1 was colocalized with in neurons and glial cells in the TCC. The S1PR1 antagonist W146 alleviated NTG-induced hyperalgesia and suppressed the upregulation of CGRP, c-fos and pSTAT3 in the TCC. Importantly, blocking S1PR1 reduced activation of microglia. In addition, we found that inhibiting STAT3 signal also attenuated NTG-induced basal mechanical and thermal hyperalgesia.

conclusionsOur results indicate that inhibiting S1PR1 signal could alleviate central sensitization and inhibit microglia activity caused by chronic NTG administration via STAT3 signal pathway, which provide a new clue for the clinical treatment of CM.

Indexed as

Migraine DisordersNitroglycerinAnimalsCentral Nervous System SensitizationDisease Models, AnimalHyperalgesiaMiceSphingosine-1-Phosphate ReceptorsNitroglycerinS1pr1 protein, mouseSphingosine-1-Phosphate ReceptorsCentral sensitizationChronic migraineMicrogliaS1PR1STAT3

Identifiers

PMID35144528
PMCPMC8903593
OpenAlexW4211254380

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.