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

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Citations (Scopus)
113 Downloads (Pure)


Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladapted central pain pathways are associated with pain chronicity following e.g. post-operative 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 patients and 29 pain-free controls, 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 components analysis of CBF identified five components that significantly discriminated chronic pain patients 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 to the pain sensitization score (r=.43, p=.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 sensitisation.

Original languageEnglish
Number of pages9
Early online date14 Feb 2020
Publication statusE-pub ahead of print - 14 Feb 2020


  • Chronic pain
  • ASL
  • Cerebral blood flow
  • PCA
  • Knee osteoarthritis
  • MRI
  • Experimental pain
  • Sensitization


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