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

Chelsea M. Kaplan* (Corresponding Author), Andrew Schrepf, Eric Ichesco, Tony Larkin, Steven E. Harte, Richard E. Harris, Alison D. Murray, Gordon D. Waiter, Daniel J. Clauw, Neil Basu

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Citation (Scopus)


OBJECTIVE: Rheumatoid arthritis (RA) patients with comorbid fibromyalgia (FM) manifest alterations in brain connectivity synonymous with central sensitization. Here we consider how peripheral inflammation, the principal nociceptive stimulus in RA, interacts with brain connectivity in RA patients with comorbid FM.

METHODS: RA patients with (FM+, n=27) and without (FM-, n=27) comorbid FM completed functional connectivity magnetic resonance imaging. Seed to whole-brain functional connectivity analyses were conducted using left mid/posterior insula and left inferior parietal lobule (IPL) seeds, regions previously linked to FM symptoms and inflammation respectively. The association between functional connectivity and erythrocyte sedimentation rate (ESR) was assessed in each FM group separately, followed by post-hoc analyses to test for interaction effects. Significance was set at a cluster-level family-wise error (FWE) rate of p < 0.05.

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

CONCLUSION: Here we provide the first neurobiological evidence that comorbid FM in RA may be linked to peripheral inflammation through pro-nociceptive patterns of brain connectivity. In patients with such 'bottom-up' pain centralization, comorbid symptoms may partially respond to anti-inflammatory treatments. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalArthritis & Rheumatology
Issue number1
Early online date26 Nov 2019
Publication statusPublished - Jan 2020

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