Large-scale brain network interactions and motor control in chronic pain: A systematic review

Farhad Rezazadeh; Shirin Aali; Parinaz Fahimi; Georgian Badicu; Farhad Rezazadeh; Shirin Aali; Parinaz Fahimi; Georgian Badicu

doi:10.3934/Neuroscience.2026025

AIMS Neuroscience

2026, Volume 13, Issue 4: 550-580. doi: 10.3934/Neuroscience.2026025

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Review

Large-scale brain network interactions and motor control in chronic pain: A systematic review

1.
Department of Sports Biomechanics, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran
2.
Department of Physical Education, Farhangian University, P.O. Box 889–14665, Tehran, Iran
3.
Department of Sports Biomechanics, Faculty of Educational Sciences and Psychology, University of Mohaghegh Ardabili, Ardabil, Iran
4.
Department of Physical Education and Special Motricity, Faculty of Physical Education and Mountain Sports, Transilvania University of Braşov, Braşov, Romania

Received: 10 May 2026 Revised: 08 August 2026 Accepted: 26 August 2026 Published: 15 October 2026

Background
Chronic pain is increasingly understood as a disorder involving maladaptive central nervous system plasticity and alterations in distributed brain networks, particularly limbic-cingulate, cerebellar, and sensorimotor networks, rather than being solely explained by persistent peripheral nociception.
Objective
This systematic review synthesized evidence on alterations in large-scale brain networks in chronic pain, including functional connectivity as well as other functional and structural neuroimaging markers involving the limbic-cingulate, cerebellar, and sensorimotor networks, and examined the available evidence regarding their potential associations with motor control and postural control related outcomes.
Methods
This review was conducted according to a prospectively developed protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261369982). Searches of PubMed, Scopus, Web of Science, PEDro, and Google Scholar (2000–2025) identified quantitative human studies that investigated large-scale brain network alterations in chronic pain. Two reviewers independently performed the study selection, data extraction, methodological quality assessment using the McMaster Critical Review Form, and risk-of-bias assessment using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Owing to substantial clinical and methodological heterogeneity, a narrative synthesis was undertaken.
Results
Eleven cross-sectional studies (805 participants) met the inclusion criteria. Chronic pain was consistently associated with altered functional connectivity in insular and cingulate regions, often extending to sensorimotor, prefrontal, and parietal areas. These changes correlated with the pain intensity. Task-based findings showed increased engagement of emotion, salience, and motor inhibition regions during pain- or movement-related contexts. A small number of studies also reported motor-related outcomes, suggesting possible sensorimotor alterations; however, objective motor control and postural measures were inconsistently assessed across studies, limiting a direct evaluation of the relationship between brain network alterations and motor function.
Conclusion
Current evidence supports a network-level perspective in which chronic pain is consistently associated with alterations in the limbic-cingulate, cerebellar, and sensorimotor networks. Nevertheless, direct evidence linking these neural alterations to objectively measured motor control and postural function remains limited and preliminary. Future longitudinal and mechanistic studies which integrate multimodal neuroimaging with standardized objective motor assessments are needed to clarify these relationships.
- chronic pain,
- motor control,
- sensorimotor network,
- functional connectivity,
- cerebellum
Citation: Farhad Rezazadeh, Shirin Aali, Parinaz Fahimi, Georgian Badicu. Large-scale brain network interactions and motor control in chronic pain: A systematic review[J]. AIMS Neuroscience, 2026, 13(4): 550-580. doi: 10.3934/Neuroscience.2026025

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Abstract

Background

Chronic pain is increasingly understood as a disorder involving maladaptive central nervous system plasticity and alterations in distributed brain networks, particularly limbic-cingulate, cerebellar, and sensorimotor networks, rather than being solely explained by persistent peripheral nociception.

Objective

This systematic review synthesized evidence on alterations in large-scale brain networks in chronic pain, including functional connectivity as well as other functional and structural neuroimaging markers involving the limbic-cingulate, cerebellar, and sensorimotor networks, and examined the available evidence regarding their potential associations with motor control and postural control related outcomes.

Methods

This review was conducted according to a prospectively developed protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420261369982). Searches of PubMed, Scopus, Web of Science, PEDro, and Google Scholar (2000–2025) identified quantitative human studies that investigated large-scale brain network alterations in chronic pain. Two reviewers independently performed the study selection, data extraction, methodological quality assessment using the McMaster Critical Review Form, and risk-of-bias assessment using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Owing to substantial clinical and methodological heterogeneity, a narrative synthesis was undertaken.

Results

Eleven cross-sectional studies (805 participants) met the inclusion criteria. Chronic pain was consistently associated with altered functional connectivity in insular and cingulate regions, often extending to sensorimotor, prefrontal, and parietal areas. These changes correlated with the pain intensity. Task-based findings showed increased engagement of emotion, salience, and motor inhibition regions during pain- or movement-related contexts. A small number of studies also reported motor-related outcomes, suggesting possible sensorimotor alterations; however, objective motor control and postural measures were inconsistently assessed across studies, limiting a direct evaluation of the relationship between brain network alterations and motor function.

Conclusion

Current evidence supports a network-level perspective in which chronic pain is consistently associated with alterations in the limbic-cingulate, cerebellar, and sensorimotor networks. Nevertheless, direct evidence linking these neural alterations to objectively measured motor control and postural function remains limited and preliminary. Future longitudinal and mechanistic studies which integrate multimodal neuroimaging with standardized objective motor assessments are needed to clarify these relationships.

Acknowledgments

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors gratefully acknowledge the editorial team for their clear guidance and adherence to submission standards, which will help expedite the review and publication process. We also thank all researchers whose work contributed to the foundation of this systematic review.

Conflict of interest

The authors declare no conflict of interest.

Authors' contributions

Conceptualization, S.A. and F.R.; Methodology, S.A. and P.F.; Software, P.F.; Validation, P.F. and G.B.; Formal analysis, S.A. and P.F.; Investigation, S.A. and P.F.; Resources, P.F.; Data Curation, P.F.; Writing – Original Draft Preparation, S.A.; Writing – Review & Editing, F.R., S.A. and G.B.; Visualization, P.F.; Supervision, F.R. and G.B.; Project Administration, F.R. All authors have read and agreed to the published version of the manuscript.

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