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. 2020 Jan;72(1):41-46.
doi: 10.1002/art.41069. Epub 2019 Nov 26.

Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia

Chelsea M Kaplan  1 , Andrew Schrepf  1 , Eric Ichesco  1 , Tony Larkin  1 , Steven E Harte  1 , Richard E Harris  1 , Alison D Murray  2 , Gordon D Waiter  2 , Daniel J Clauw  1 , Neil Basu  3
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Free article

Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia

Chelsea M Kaplan et al. Arthritis Rheumatol. 2020 Jan.
Free article

Abstract

Objective: Rheumatoid arthritis (RA) patients with concomitant fibromyalgia (FM) exhibit alterations in brain connectivity synonymous with central sensitization. This study was undertaken to investigate how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with FM.

Methods: RA patients with concomitant FM and those without FM (FM+ and FM-, respectively; n = 27 per group) underwent functional connectivity magnetic resonance imaging. Seed-to-whole-brain functional connectivity analyses were conducted using seeds from the left mid/posterior insula and left inferior parietal lobule (IPL), which are regions that have been previously linked to FM symptoms and inflammation, respectively. The association between functional connectivity and erythrocyte sedimentation rate (ESR) was assessed in each group separately, followed by post hoc analyses to test for interaction effects. Cluster-level, family-wise error (FWE) rates were considered significant if the P value was less than 0.05.

Results: The group of RA patients with FM and those without FM did not differ by age, sex, or ESR (P > 0.2). In FM+ RA patients, increased functional connectivity of the insula-left IPL, left IPL-dorsal anterior cingulate, and left IPL-medial prefrontal cortex regions correlated with higher levels of ESR (all FWE-corrected P < 0.05). Post hoc interaction analyses largely confirmed the relationship between ESR and connectivity changes as FM scores increased.

Conclusion: We report the first neurobiologic evidence that FM in RA may be linked to peripheral inflammation via pronociceptive patterns of brain connectivity. In patients with such "bottom-up" pain centralization, concomitant symptoms may partially respond to antiinflammatory treatments.

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References

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    1. Basu N, Kaplan CM, Ichesco E, Larkin T, Harris RE, Murray A, et al. Neurobiologic features of fibromyalgia are also present among rheumatoid arthritis patients. Arthritis Rheumatol 2018;70:1000-7.
    1. Harte SE, Harris RE, Clauw DJ. The neurobiology of central sensitization. J Appl Biobehav Res 2018;23:e12137.
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