Many patients with rheumatoid arthritis (RA) report pain despite excellent control of inflammation with immunotherapies. Variable degrees of coexisting fibromyalgia (FM) may explain this disparity. FM has been characterized by aberrant brain functional connectivity, especially between the default mode network (DMN) and insula. We undertook this study to test the hypothesis that RA patients with the highest 2011 American College of Rheumatology FM survey criteria scores-a continuous measure of the degree of FM also known as "fibromyalgianess" (FMness)-would demonstrate functional connectivity abnormalities similar to those in FM.
RA patients underwent an 11-minute functional connectivity magnetic resonance imaging (MRI) brain scan and a clinical evaluation which included a measure of FMness. Brain networks were isolated from functional connectivity MRI data. Individual patient network-to-whole brain connectivity analyses were then conducted, followed by group-level regression, which correlated the connectivity of each network with FMness. Results were significant on the cluster level with a family-wise error (FWE) rate P value less than 0.05 derived from an uncorrected voxel-level P value less than 0.001.
A total of 54 patients participated (mean age 54.9 years, 75.9% women, mean FMness score 13.2 [range 1-29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r = 0.58, FWE-corrected P = 0.001) was demonstrated.
RA patients who have increased levels of FMness appear to share neurobiologic features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients' symptoms being related to the central nervous system rather than to classic inflammatory mechanisms.