Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with Rheumatoid Arthritis

Abstract

Background: Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA.Methods: 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity.Results: When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters.Conclusion: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.

The Mesolimbic Dopamine System in Chronic Pain and Associated Affective Comorbidities

“…The PFC is a major component of the mesolimbic circuit, which affects several structures involved in pain perception, motivational drive, substance seeking, and anxiodepressive states (55)(56)(57)(58)(59)(60)(61). A resting-state functional magnetic resonance imaging study with patients with rheumatoid arthritis revealed that prolonged pain states are associated with increased connectivity between the insula and the PFC (62). Using functional magnetic resonance imaging, Baliki et al demonstrated that chronic back pain results in increased PFC activity, and this activity is strongly related to pain intensity (63).…”

Altered Primary Motor Cortex Structure, Organization, and Function in Chronic Pain: A Systematic Review and Meta-Analysis

“…Several studies included in this review investigated the sensorimotor cortex rather than the M1. [23][24][25]37,102 It is possible that heterogeneity in the brain region being investigated (ie, sensorimotor vs M1) contributed to the inconclusive findings of this review.…”

Sustained perturbation in functional connectivity induced by cold pain

“…Increased SN -DMN connectivity is also a result widely reported within the chronic pain literature. For example, increased connectivity between the DMN and the insula has been described in patients with diabetic neuropathic pain (Chen et al, 2013) and patients with rheumatoid arthritis (Flodin et al, 2016). Increased insula-DMN coupling decreases after treatment in fibromyalgia patients and is associated with a reduction in pain (Napadow et al, 2010).…”