Relations Between Brain Alterations and Clinical Pain Measures in Chronic Musculoskeletal Pain: A Systematic Review

Iris Coppieters, Mira Meeus, Jeroen Kregel, Karen Caeyenberghs, Robby De Pauw, Dorien Goubert, Barbara Cagnie

Research output: Contribution to journalScientific reviewpeer-review

77 Citations (Scopus)


UNLABELLED: Compelling evidence has shown chronic widespread and exaggerated pain experience in chronic musculoskeletal pain (MSKP) conditions. In addition, neuroimaging research has revealed morphological and functional brain alterations in these patients. It is hypothesized that brain alterations play a role in the persistent pain complaints of patients with chronic MSKP. Nevertheless, lack of overview exists regarding the relations between brain alterations and clinical measures of pain. The present systematic review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, to investigate the relations between structural or functional brain alterations, using magnetic resonance imaging scans, and clinical pain measures in patients with chronic MSKP. PubMed, Web of Science, Cinahl, and Cochrane databases were searched. First, the obtained articles were screened according to title and abstract. Second, the screening was on the basis of full-text. Risk of bias in included studies was investigated according to the modified Newcastle-Ottawa Scale. Twenty studies met the inclusion criteria. Moderate evidence shows that higher pain intensity and pressure pain sensitivity are related to decreased regional gray matter (GM) volume in brain regions encompassing the cingulate cortex, the insula, and the superior frontal and temporal gyrus. Further, some evidence exists that longer disease duration in fibromyalgia is correlated with decreased total GM volume. Yet, inconclusive evidence exists regarding the association of longer disease duration with decreased or increased regional GM volume in other chronic MSKP conditions. Inconclusive evidence was found regarding the direction of the relation of pain intensity and pressure pain sensitivity with microstructural white matter and functional connectivity alterations. In conclusion, preliminary to moderate evidence demonstrates relations between clinical pain measures, and structural and functional connectivity alterations within brain regions involved in somatosensory, affective, and cognitive processing of pain in chronic MSKP. Nevertheless, inconclusive results exist regarding the direction of these relations. Further research is warranted to unravel whether these brain alterations are positively or negatively correlated to clinical pain measures.

PERSPECTIVE: Structural and functional brain alterations within regions involved in somatosensory, affective, and cognitive pain processing play a crucial role in the persistent pain of chronic MSKP patients. Accordingly, these brain alterations have to be taken into account when assessing and treating patients with chronic MSKP.

Original languageEnglish
Pages (from-to)949-962
Number of pages14
JournalThe Journal of Pain
Issue number9
Publication statusPublished - Sep 2016

Bibliographical note

Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.


  • Brain/diagnostic imaging
  • Chronic Pain
  • Databases, Bibliographic/statistics & numerical data
  • Humans
  • Magnetic Resonance Imaging
  • Musculoskeletal Pain/diagnosis
  • Pain Measurement/methods


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