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

Abstract

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
Volume72
Issue number1
Early online date26 Nov 2019
DOIs
Publication statusPublished - Jan 2020

Fingerprint

Fibromyalgia
Rheumatoid Arthritis
Inflammation
Brain
Parietal Lobe
Blood Sedimentation
Seeds
Central Nervous System Sensitization
Gyrus Cinguli
Prefrontal Cortex
Anti-Inflammatory Agents
Magnetic Resonance Imaging
Pain

Cite this

Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia. / Kaplan, Chelsea M. (Corresponding Author); Schrepf, Andrew; Ichesco, Eric; Larkin, Tony; Harte, Steven E.; Harris, Richard E.; Murray, Alison D.; Waiter, Gordon D.; Clauw, Daniel J.; Basu, Neil.

In: Arthritis & Rheumatology, Vol. 72, No. 1, 01.2020, p. 41-46.

Research output: Contribution to journalArticle

Kaplan, Chelsea M. ; Schrepf, Andrew ; Ichesco, Eric ; Larkin, Tony ; Harte, Steven E. ; Harris, Richard E. ; Murray, Alison D. ; Waiter, Gordon D. ; Clauw, Daniel J. ; Basu, Neil. / Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia. In: Arthritis & Rheumatology. 2020 ; Vol. 72, No. 1. pp. 41-46.
@article{838bb7d5a61d47b4b9084399c75a7f4d,
title = "Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia",
abstract = "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.",
author = "Kaplan, {Chelsea M.} and Andrew Schrepf and Eric Ichesco and Tony Larkin and Harte, {Steven E.} and Harris, {Richard E.} and Murray, {Alison D.} and Waiter, {Gordon D.} and Clauw, {Daniel J.} and Neil Basu",
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.",
year = "2020",
month = "1",
doi = "10.1002/art.41069",
language = "English",
volume = "72",
pages = "41--46",
journal = "Arthritis & Rheumatology",
issn = "2326-5191",
publisher = "Wiley",
number = "1",

}

TY - JOUR

T1 - Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia

AU - Kaplan, Chelsea M.

AU - Schrepf, Andrew

AU - Ichesco, Eric

AU - Larkin, Tony

AU - Harte, Steven E.

AU - Harris, Richard E.

AU - Murray, Alison D.

AU - Waiter, Gordon D.

AU - Clauw, Daniel J.

AU - Basu, Neil

N1 - 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.

PY - 2020/1

Y1 - 2020/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85075723947&partnerID=8YFLogxK

U2 - 10.1002/art.41069

DO - 10.1002/art.41069

M3 - Article

C2 - 31379121

VL - 72

SP - 41

EP - 46

JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

SN - 2326-5191

IS - 1

ER -