Evidence map›Paper›PMID 30400767›Full record

ArticleThe journal of headache and pain2018

NR2B-Tyr phosphorylation regulates synaptic plasticity in central sensitization in a chronic migraine rat model.

Xue-Ying Wang, Hui-Ru Zhou, Sha Wang, Chao-Yang Liu, Guang-Cheng Qin, Qing-Qing Fu, Ji-Ying Zhou, Li-Xue Chen

Open access · goldAbstract read
In one paragraph

Article in The journal of headache and pain, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

45 citing papers in PubMed, 75 citations in OpenAlex.

  1. Hemiplegic migraine: genetics and pathophysiology.The Journal of clinical investigation · 2026
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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

8 authors at 1 institution in 1 country.

Xue-Ying WangLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
Hui-Ru ZhouLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
Sha WangLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
Chao-Yang LiuLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
Guang-Cheng QinLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
Qing-Qing FuLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China.
Ji-Ying ZhouDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Li-Xue ChenLaboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 1st You Yi Road, Yu Zhong District, Chongqing, 400016, China. chenlixue@hospital.cqmu.edu.cn.ORCID http://orcid.org/0000-0001-8213-8828
The Affiliated Yongchuan Hospital of Chongqing Medical University · CN

Funding

District Science and Technology Projects of Yuzhong Chongqin 20160107National Natural Science Foundation of China 81671092National Natural Science Foundation of China 81671093
6 · The paper itself

Abstract

backgroundAlthough the mechanism of chronic migraine (CM) is unclear, it might be related to central sensitization and neuronal persistent hyperexcitability. The tyrosine phosphorylation of NR2B (NR2B-pTyr) reportedly contributes to the development of central sensitization and persistent pain in the spinal cord. Central sensitization is thought to be associated with an increase in synaptic efficiency, but the mechanism through which NR2B-pTyr regulates synaptic participation in CM-related central sensitization is unknown. In this study, we aim to investigate the role of NR2B-pTyr in regulating synaptic plasticity in CM-related central sensitization.

methodsMale Sprague-Dawley rats were subjected to seven inflammatory soup (IS) injections to model recurrent trigeminovascular or dural nociceptor activation, which is assumed to occur in patients with CM. We used the von Frey test to detect changes in mechanical withdrawal thresholds, and western blotting and immunofluorescence staining assays were performed to detect the expression of NR2B-pTyr in the trigeminal nucleus caudalis (TNC). NR2B-pTyr was blocked with the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-(t-butyl)-pyrazolo [3,4-d] pyrimidine (PP2) and the protein tyrosine kinase inhibitor genistein to detected the changes in calcitonin gene-related peptide (CGRP), substance P (SP), and the synaptic proteins postsynaptic density 95 (PSD95), synaptophysin (Syp), synaptotagmin1 (Syt-1). The synaptic ultrastructures were observed by transmission electron microscopy (TEM), and the dendritic architecture of TNC neurons was observed by Golgi-Cox staining.

resultsStatistical analyses revealed that repeated infusions of IS induced mechanical allodynia and significantly increased the expression of NR2B Tyr-1472 phosphorylation (pNR2B-Y1472) and NR2B Tyr-1252 phosphorylation (pNR2B-Y1252) in the TNC. Furthermore, the inhibition of NR2B-pTyr by PP2 and genistein relieved allodynia and reduced the expression of CGRP, SP, PSD95, Syp and Syt-1 and synaptic transmission.

conclusionsThese data indicate that NR2B-pTyr might regulate synaptic plasticity in central sensitization in a CM rat model. The inhibition of NR2B tyrosine phosphorylation has a protective effect on threshold dysfunction and migraine attacks through the regulation of synaptic plasticity in central sensitization.

Indexed as

Disease Models, AnimalAnimalsCentral Nervous System SensitizationHyperalgesiaMaleMigraine DisordersNeuronal PlasticityNeuronsPainPhosphorylationRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateTrigeminal Caudal NucleusTyrosineNR2B NMDA receptorReceptors, N-Methyl-D-AspartateTyrosineCentral sensitizationChronic migraineGolgi-cox stainingNR2B-Tyr phosphorylationSynaptic plasticityTEM

Identifiers

PMID30400767
PMCPMC6755586
OpenAlexW2900142338

What OpenQuestion holds

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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.