Background/Purpose:

Many rheumatoid arthritis (RA) patients continue to report pain despite excellent control of inflammation with immunotherapy regimes. Variable degrees of co-existing fibromyalgia (FM) may explain this disparity.

Patients diagnosed with FM are characterised by features of pain centralisation. For example they exhibit aberrant inter-regional brain communications, as measured by functional connectivity MRI (fcMRI). We and others have suggested that part of the neural signature for pain centralisation is enhanced connectivity between the insula (a region implicated in the affective processing of pain) and the Default Mode Network (DMN, a network related to self-referential thinking).

We hypothesised that RA patients reporting the highest 2011 ACR FM survey criteria scores – a continuous measure of FM degree also known as fibromyalgianess (FMness) – would demonstrate fcMRI features of pain centralisation as observed in FM.

Methods:

Consecutive clinic attending RA patients fulfilling ACR/EULAR 2012 criteria were recruited and underwent a 9min fcMRI brain scan. In addition, they undertook a clinical evaluation which included a measure of FMness (ACR FM survey criteria) and inflammation (CRP). Images were acquired by a 3 Tesla, 8 channel phased array head coil using a T2*-weighted gradient-echo echo-planar imaging pulse sequence. FcMRI data were preprocessed and analyzed using SPM8, Conn and GIFT running on MATLAB 7.10. Group independent component analysis selected out the brain networks of interest (DMN, salience, dorsal attention, sensorimotor). Network to whole brain functional connectivity analyses were then conducted for each patient followed by group level multiple linear regression which correlated connectivity of each network to FMness. Finally, corrections for age, sex and CRP were applied. Analyses were significant on the cluster level with a false discovery rate p value <0.05 derived from an uncorrected voxel level p value <0.001.

Results:

54 patients participated (mean age 54.9years; 75.9% female; mean disease duration 11.5 years; mean FMness score 13.3 [range 1-29]; mean DAS28 3.6 [range 1.5-6.4]). They demonstrated a significant (p=0.002) positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r=0.55). This observation remained significant after adjusting for age, sex and CRP. No other significant functional connections were identified with the DMN or among the other selected networks.

Conclusion:

Rheumatoid arthritis patients who report high levels of FMness appear to share neurobiological features with ‘primary’ FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state with a centralised pain component (which demands alternative therapeutic strategies to standard RA immunotherapies). The ACR FM survey appears to be a strong surrogate for neurobiological evidence of centralised pain and, in the future, could be a useful tool to support clinicans’ evaluation of pain and subsequent personalised management.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/brain-functional-connectivity-features-of-pain-centralisation-relate-to-degree-of-fibromyalgianess-in-rheumatoid-arthritis/