Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies

Background: Resting-state functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity (FC) of the insula (INS) in patients with musculoskeletal pain (MSP). However, there is a lack of consistency in previous studies, which is an obstacle to understanding the unde...

Full description

Saved in:
Bibliographic Details
Main Authors: Peng Lai, Xingyao Chen, Jiacheng Liu, Zilei Tian, Yangke Mao, Chenyang Jia, Siting Ma, Deliang Zhu, Ming Xin, Fang Zeng, Shirui Cheng
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Brain Research Bulletin
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025001066
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850059840011894784
author Peng Lai
Xingyao Chen
Jiacheng Liu
Zilei Tian
Yangke Mao
Chenyang Jia
Siting Ma
Deliang Zhu
Ming Xin
Fang Zeng
Shirui Cheng
author_facet Peng Lai
Xingyao Chen
Jiacheng Liu
Zilei Tian
Yangke Mao
Chenyang Jia
Siting Ma
Deliang Zhu
Ming Xin
Fang Zeng
Shirui Cheng
author_sort Peng Lai
collection DOAJ
description Background: Resting-state functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity (FC) of the insula (INS) in patients with musculoskeletal pain (MSP). However, there is a lack of consistency in previous studies, which is an obstacle to understanding the underlying neuropathology of MSP. Method: Seven databases, including PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP, were systematically searched from inception to 15 May 2024. The meta-analysis of the aberrant INS-based FC in MSP patients was performed using the anisotropic effect-size signed differential mapping (AES-SDM). Results: A total of eleven neuroimaging studies with 276 patients and 253 HCs were included in the meta-analysis. The results indicate that MSP patients have increased FC between INS and the right median cingulate gyri, right inferior frontal gyrus, right paracentral lobule, and right supplementary motor area, and decreased FC between INS and the right posterior cingulate gyrus, left precuneus, and left angular gyrus. Heterogeneity and sensitivity analysis showed that most of the results of INS-based FC were highly reproducible and robust. Meta-regression analysis showed that revealed a negative association between the Visual Analog Scale (VAS) score and the reduction in FC between the INS and the left precuneus. Conclusion: The meta-analysis reveals that patients with MSP show abnormal FC between the INS and multiple brain regions, which are involved in emotional, cognitive, sensory, visuospatial and motor regulation of pain. These findings provide important insights into the underlying neuropathological mechanisms of musculoskeletal disorders.
format Article
id doaj-art-1f99173cbb4a431cbc79e7ad38580741
institution DOAJ
issn 1873-2747
language English
publishDate 2025-05-01
publisher Elsevier
record_format Article
series Brain Research Bulletin
spelling doaj-art-1f99173cbb4a431cbc79e7ad385807412025-08-20T02:50:45ZengElsevierBrain Research Bulletin1873-27472025-05-0122411129410.1016/j.brainresbull.2025.111294Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studiesPeng Lai0Xingyao Chen1Jiacheng Liu2Zilei Tian3Yangke Mao4Chenyang Jia5Siting Ma6Deliang Zhu7Ming Xin8Fang Zeng9Shirui Cheng10Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, ChinaHospital of Chengdu University of Traditional Chinese Medicine, School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, ChinaGeriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Department of Rehabilitation, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu 611130, ChinaGeriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Department of Rehabilitation, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu 611130, ChinaAcupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, China; Corresponding authors at: Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Acupuncture & Brain Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, China; Corresponding authors at: Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.Background: Resting-state functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity (FC) of the insula (INS) in patients with musculoskeletal pain (MSP). However, there is a lack of consistency in previous studies, which is an obstacle to understanding the underlying neuropathology of MSP. Method: Seven databases, including PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chongqing VIP, were systematically searched from inception to 15 May 2024. The meta-analysis of the aberrant INS-based FC in MSP patients was performed using the anisotropic effect-size signed differential mapping (AES-SDM). Results: A total of eleven neuroimaging studies with 276 patients and 253 HCs were included in the meta-analysis. The results indicate that MSP patients have increased FC between INS and the right median cingulate gyri, right inferior frontal gyrus, right paracentral lobule, and right supplementary motor area, and decreased FC between INS and the right posterior cingulate gyrus, left precuneus, and left angular gyrus. Heterogeneity and sensitivity analysis showed that most of the results of INS-based FC were highly reproducible and robust. Meta-regression analysis showed that revealed a negative association between the Visual Analog Scale (VAS) score and the reduction in FC between the INS and the left precuneus. Conclusion: The meta-analysis reveals that patients with MSP show abnormal FC between the INS and multiple brain regions, which are involved in emotional, cognitive, sensory, visuospatial and motor regulation of pain. These findings provide important insights into the underlying neuropathological mechanisms of musculoskeletal disorders.http://www.sciencedirect.com/science/article/pii/S0361923025001066Musculoskeletal painInsulaFunctional connectivityMeta-analysisFunctional magnetic resonance imaging
spellingShingle Peng Lai
Xingyao Chen
Jiacheng Liu
Zilei Tian
Yangke Mao
Chenyang Jia
Siting Ma
Deliang Zhu
Ming Xin
Fang Zeng
Shirui Cheng
Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies
Brain Research Bulletin
Musculoskeletal pain
Insula
Functional connectivity
Meta-analysis
Functional magnetic resonance imaging
title Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies
title_full Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies
title_fullStr Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies
title_full_unstemmed Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies
title_short Abnormalities of insular functional connectivity in patients with musculoskeletal pain: A meta-analysis of resting-state fMRI studies
title_sort abnormalities of insular functional connectivity in patients with musculoskeletal pain a meta analysis of resting state fmri studies
topic Musculoskeletal pain
Insula
Functional connectivity
Meta-analysis
Functional magnetic resonance imaging
url http://www.sciencedirect.com/science/article/pii/S0361923025001066
work_keys_str_mv AT penglai abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT xingyaochen abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT jiachengliu abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT zileitian abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT yangkemao abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT chenyangjia abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT sitingma abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT deliangzhu abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT mingxin abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT fangzeng abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies
AT shiruicheng abnormalitiesofinsularfunctionalconnectivityinpatientswithmusculoskeletalpainametaanalysisofrestingstatefmristudies