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Brain perfusion patterns are altered in chronic knee pain: a spatial covariance analysis of arterial spin labelling MRI

Iwabuchi, Sarina J.; Xing, Yue; Cottam, William J.; Drabek, Marianne M.; Tadjibaev, Arman; Fernandes, Gwen S.; Petersen, Kristian K.; Arendt-Nielsen, Lars; Graven-Nielsen, Thomas; Valdes, Ana M.; Zhang, Weiya; Doherty, Michael; Walsh, David; Auer, Dorothee P.


Sarina J. Iwabuchi

Research Fellow

Arman Tadjibaev

Gwen S. Fernandes

Kristian K. Petersen

Lars Arendt-Nielsen

Thomas Graven-Nielsen

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Professor of Molecular & Genetic Epidemiology

Michael Doherty

Professor of Rheumatology


Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladapted central pain pathways are associated with pain chronicity, for example, in postoperative pain after knee replacement. Other factors such as low mood, anxiety, and tendency to catastrophize are also important contributors. We aimed to investigate brain imaging features that underpin pain chronicity based on multivariate pattern analysis of cerebral blood flow (CBF), as a marker of maladaptive brain changes. This was achieved by identifying CBF patterns that discriminate chronic pain from pain-free conditions and by exploring their explanatory power for factors thought to drive pain chronification. In 44 chronic knee pain and 29 pain-free participants, we acquired both CBF and T1-weighted data. Participants completed questionnaires related to affective processes and pressure and cuff algometry to assess pain sensitization. Two factor scores were extracted from these scores representing negative affect and pain sensitization. A spatial covariance principal component analysis of CBF identified 5 components that significantly discriminated chronic pain participants from controls, with the unified network achieving 0.83 discriminatory accuracy (area under the curve). In chronic knee pain, significant patterns of relative hypoperfusion were evident in anterior default-mode and salience network hubs, while hyperperfusion was seen in posterior default mode, thalamus, and sensory regions. One component correlated positively with the pain sensitization score (r = 0.43, P = 0.006), suggesting that this CBF pattern reflects neural activity changes encoding pain sensitization. Here, we report a distinct chronic knee pain-related representation of CBF, pointing toward a brain signature underpinning central aspects of pain sensitization.


Iwabuchi, S. J., Xing, Y., Cottam, W. J., Drabek, M. M., Tadjibaev, A., Fernandes, G. S., …Auer, D. P. (2020). Brain perfusion patterns are altered in chronic knee pain: a spatial covariance analysis of arterial spin labelling MRI. PAIN, 161(6), 1255-1263.

Journal Article Type Article
Acceptance Date Feb 4, 2020
Online Publication Date Feb 14, 2020
Publication Date Feb 14, 2020
Deposit Date Feb 13, 2020
Publicly Available Date Feb 15, 2021
Journal Pain
Print ISSN 0304-3959
Electronic ISSN 1872-6623
Publisher Lippincott, Williams & Wilkins
Peer Reviewed Peer Reviewed
Volume 161
Issue 6
Pages 1255-1263
Keywords Anesthesiology and Pain Medicine; Neurology; Clinical Neurology
Public URL
Publisher URL
Additional Information Iwabuchi, Sarina J.a,b,c; Xing, Yueb,c; Cottam, William J.a,b,c; Drabek, Marianne M.a,b,c; Tadjibaev, Armana,b,c; Fernandes, Gwen S.a,d; Petersen, Kristian K.e,f; Arendt-Nielsen, Larse,f; Graven-Nielsen, Thomasf; Valdes, Ana M.a,b,d; Zhang, Weiyaa,b,d; Doherty, Michaela,b,d; Walsh, Davida,b,d; Auer, Dorothee P.a,b,c,* Brain perfusion patterns are altered in chronic knee pain: a spatial covariance analysis of arterial spin labelling MRI, PAIN: June 2020 - Volume 161 - Issue 6 - p 1255-1263 doi: 10.1097/j.pain.0000000000001829


Iwabuchi Et Al 2020 (383 Kb)

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Copyright Statement
This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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