Evidence map›Paper›PMID 40652178›Full record

ArticleBMC anesthesiology2025

Bromodomain-containing protein 4 contributes to chronic postsurgical pain via activating TLR4/NF-kappaB-dependent neuroinflammation.

Ruichen Shu, Yuan Li, Zengli Zhang, Xuan Zhang, Shan Guan, Kaiyuan Wang, Yiqing Yin

Abstract read
In one paragraph

Article in BMC anesthesiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. 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

7 authors.

Ruichen ShuDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
Yuan LiDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
Zengli ZhangDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
Xuan ZhangDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
Shan GuanDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
Kaiyuan WangDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China.
Yiqing YinDepartment of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Huanhu West Road, Tianjin, 300060, China. yinyiqing@tmu.edu.cn.

Funding

National Natural Science Foundation of China 81801889National Natural Science Foundation of China 82001479National Natural Science Foundation of China 82101351Tianjin Municipal Science and Technology Plan Project 22JCQNJC01050
6 · The paper itself

Abstract

backgroundChronic pain affects 1.5 billion individuals worldwide but remains woefully undertreated, particularly occurring in the populations undergoing surgical procedures. Increasing evidence indicates that epigenetic modifications are involved in the pathogenesis of chronic pain. This study aimed to investigate the role of bromodomain-containing protein 4 (Brd4) in chronification of pain after surgery.

methodsMale Sprague-Dawley rats were subjected to skin/muscle incision and retraction surgery to induce chronic postsurgical pain. Nociceptive thresholds and locomotor activity were assessed. The spinal cord was collected to detect the expressions of Brd4, toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) pathway, and proinflammatory cytokines and chemokines release. The BET inhibitor JQ1 was used to verify the contribution of Brd4 to chronic postsurgical pain.

resultsSignificant upregulation of spinal Brd4 expression, accompanied by activation of the TLR4/NF-κB signaling cascade and increased release of proinflammatory mediators were presented in the rat model of chronic postsurgical pain. The BET inhibitor JQ1 prevented the development of chronic postsurgical pain in a dose-dependent manner. Moreover, JQ1 obviously suppressed the activation of TLR4 and the phosphorylation and translocation of NF-κB as well as subsequently cytokines and chemokines release, including IL-1β, IL-6, TNF-α, CXCL1, CXCL2 and CCL2.

conclusionsThe epigenetic regulator Brd4 initiates neuroinflammation in spinal cord through activating TLR4/NF-κB signaling pathway and enhancing cytokine and chemokines release, thereby contributing to the transition to chronic postsurgical pain. JQ1 halts chronic pain development, providing a novel therapy for patients at high risk of persistent pain.

Indexed as

Chronic PainNeuroinflammatory DiseasesNF-kappa BPostoperative PainToll-Like Receptor 4Transcription FactorsAnimalsAzepinesBromodomain Containing ProteinsCell Cycle ProteinsDisease Models, AnimalMaleNuclear ProteinsRatsRats, Sprague-DawleySpinal CordAzepinesBrd4 protein, ratBromodomain Containing ProteinsCell Cycle Proteins(+)-JQ1 compoundNF-kappa BNuclear ProteinsTlr4 protein, ratToll-Like Receptor 4Transcription FactorsTriazolesBrd4Chronic postsurgical painEpigeneticsNeuroinflammationNF-κB

Identifiers

PMID40652178
PMCPMC12254965

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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.