Inflammation is associated with pro-nociceptive 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

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
JournalArthritis & Rheumatology
Early online date5 Aug 2019
DOIs
Publication statusE-pub ahead of print - 5 Aug 2019

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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

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Inflammation is associated with pro-nociceptive 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, 05.08.2019.

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. / Inflammation is associated with pro-nociceptive brain connections in rheumatoid arthritis patients with concomitant fibromyalgia. In: Arthritis & Rheumatology. 2019.
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title = "Inflammation is associated with pro-nociceptive 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.",
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T1 - Inflammation is associated with pro-nociceptive 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 - 2019/8/5

Y1 - 2019/8/5

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.mendeley.com/research/inflammation-associated-pronociceptive-brain-connections-rheumatoid-arthritis-patients-concomitant-f

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DO - 10.1002/art.41069

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JO - Arthritis & Rheumatology

JF - Arthritis & Rheumatology

SN - 2326-5191

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