Towards a brain signature of chronic pain using cerebral blood flow spatial covariance analysis in people with chronic knee pain

Chronic musculoskeletal pain is a common problem globally. Current evidence suggests that maladaptive modulation of central pain pathways is associated with pain chronicity following e.g. chronic post-operative pain after knee replacement. Other factors such as low mood, anxiety and tendency to catastrophize seem to also be important contributors. We aimed to identify a chronic pain brain signature that discriminates chronic pain from pain-free conditions using cerebral blood flow (CBF) measures, and explore how this signature relates to the chronic pain experience. In 44 chronic knee pain patients and 29 pain-free controls, we acquired CBF data (using arterial spin labelling) and T1-weighted images. Participants completed a series of 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, respectively. 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 hypo-perfusion were evident in anterior regions of the default mode and salience network hubs, while hyperperfusion was seen in posterior default mode regions, the thalamus, and sensory regions. One component was positively correlated to the pain sensitization score (r=.43, p=.006), suggesting that this CBF pattern reflects the neural activity changes encoding pain sensitization. Here, we report the first chronic knee pain-related brain signature, pointing to a brain signature underpinning the central aspects of pain sensitisation.