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 journalArticlepeer-review

22 Citations (Scopus)
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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.

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

Bibliographical note

Financial Support: This study was supported by Pfizer.

Acknowledgements: Special thanks to the patients who volunteered to be part of this research effort and thank you to Mariella D’Allesandro for help with recruitment and data collection.


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