Brain Structural and Functional Alterations in Regions of Pain-processing in Individuals with Rheumatoid Arthritis
Catherine Chong1, Juna Musa2, Cynthia Crowson1, Anushka Irani2, Todd Schwedt1, Kirk Welker2, John Davis1
1Mayo Clinic, 2Neurology, Mayo Clinic
Objective:
This study examined alterations in brain structure and resting-state functional connectivity (rs-fMRI) in Rheumatoid Arthritis (RA) compared to healthy controls (HC) and explored relationships with disease activity.
Background:
RA is a chronic autoimmune disease associated with joint inflammation and systemic manifestations. Despite effective disease-modifying antirheumatic drugs many patients report persistent pain disproportionate to inflammation, suggesting central sensitization and nociplastic mechanisms.
Design/Methods:
Individuals with RA and HC were prospectively enrolled. All participants completed the Clinical Disease Activity Index questionnaire (CDAI) to assess RA disease severity and underwent brain structural (T1-weighted) and resting-state functional MRI (rs-fMRI). Functional connectivity was evaluated across 63 a priori defined pain-related brain regions, with results corrected for multiple comparisons (FDR). Group differences were analyzed using ANOVA models adjusted for age and sex.
Results:
This study included 10 individuals with RA (mean age= 58.3; SD=11.6; 9 females/1 male) and 11 HC (mean age= 56.7; SD=10.2; 9 females/2 males). Nine individuals with RA completed the CDAI (mean score=19.1, SD=15.2). Compared to HC, RA patients showed stronger connectivity between the right primary somatosensory cortex and right supramarginal gyrus, and between the left lateral parietal cortex and left lingual gyrus. RA patients had smaller bilateral thalamus, left amygdala, right choroid plexus, and central cingulate volume, and greater right insula volume (all p<0.05, uncorrected for multiple comparisons). Within RA, higher CDAI scores correlate with stronger connectivity between the left supramarginal and left middle cingulate cortex.
Conclusions:
Individuals with RA demonstrated functional and structural reorganization of key pain-processing regions, including networks involved in sensory-discriminative processes and visual-sensory integration. Correlations of higher disease activity with stronger fc between the left supramarginal and middle cingulate is consistent with the role of the cingulate in pain attention and appraisal. These findings highlight widespread reorganization of nociceptive and cognitive-affective processes in RA.
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