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.
Highlights
Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease that primarily affects the joints
It is reasonable to stipulate that the long-term pain in RA may be accompanied by altered cerebral pain processing, which is indirectly supported by previous studies showing a generalized increase in pain sensitivity in RA patients compared to controls (Leffler et al, 2002; Fridén et al, 2013)
We observed significantly increased pressure pain sensitivity at the affected finger joints (i.e., P50 joint) in RA patients compared to controls t(41) = −3.85, p = 0.0002
Summary
Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease that primarily affects the joints. In line with our previous studies of altered resting-state connectivity (Flodin et al, 2014) and abnormal cerebral pain processing in fibromyalgia patients (Jensen et al, 2009), a limited number of studies have investigated pain processing in RA populations. Schweinhardt et al (2008) on the other hand, found correlations between pain evoked brain activity in the medial prefrontal cortex (MPFC) and depressive symptoms in RA patients. To our knowledge, the current study is among the first to investigate spontaneous fluctuation of brain activity in canonical pain brain regions among RA patients using resting state fMRI. Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. We investigated resting-state brain connectivity associated with prolonged pain in RA
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