Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients

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

Research output: Contribution to journalArticle

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Abstract

Objectives: Many rheumatoid arthritis (RA) patients report pain despite excellent control of inflammation with immunotherapies. Variable degrees of co-existing fibromyalgia (FM) may explain this disparity. FM has been characterised by aberrant brain functional connectivity, especially between the Default Mode Network (DMN) and insula. We hypothesised that RA patients reporting the highest 2011 ACR FM survey criteria scores- a continuous measure of FM degree also known as fibromyalgianess (FMness)- would demonstrate functional connectivity abnormalities similar to FM. Methods: RA patients underwent an 11 min functional connectivity MRI brain scan (fcMRI) and a clinical evaluation which included a measure of FMness. Brain networks were isolated from FcMRI data. Individual patient network to whole brain connectivity analyses were then conducted followed by group level regression which correlated the connectivity of each network with FMness. Results were significant on the cluster level with a family wise error (FWE) rate p-value <0.05 derived from an uncorrected voxel level p-value <0.001. Results: 54 patients participated (mean age 54.9years; 75.9% female; mean FMness score 13.3 [range 1-29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r=0.58, p=0.001 FWE) was demonstrated. Conclusions: RA patients who have increased levels of FMness appear to share neurobiological features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients’ symptoms being related to CNS rather than classic inflammatory mechanisms.
Original languageEnglish
Pages (from-to)1000-1007
Number of pages8
JournalArthritis & Rheumatology
Volume70
Issue number7
Early online date11 May 2018
DOIs
Publication statusPublished - Jul 2018

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Fibromyalgia
Rheumatoid Arthritis
Brain
Magnetic Resonance Imaging
Pain
Neuroimaging
Immunotherapy
Inflammation

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Basu, N., Kaplan, C. M., Ichesco, E., Larkin, T., Harris, R. E., Murray, A., ... Clauw, D. J. (2018). Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients. Arthritis & Rheumatology, 70(7), 1000-1007. https://doi.org/10.1002/art.40451

Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients. / Basu, Neil (Corresponding Author); Kaplan, Chelsea M.; Ichesco, Eric; Larkin, Tony; Harris, Richard E.; Murray, Alison; Waiter, Gordon; Clauw, Daniel J.

In: Arthritis & Rheumatology, Vol. 70, No. 7, 07.2018, p. 1000-1007.

Research output: Contribution to journalArticle

Basu, Neil ; Kaplan, Chelsea M. ; Ichesco, Eric ; Larkin, Tony ; Harris, Richard E. ; Murray, Alison ; Waiter, Gordon ; Clauw, Daniel J. / Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients. In: Arthritis & Rheumatology. 2018 ; Vol. 70, No. 7. pp. 1000-1007.
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title = "Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients",
abstract = "Objectives: Many rheumatoid arthritis (RA) patients report pain despite excellent control of inflammation with immunotherapies. Variable degrees of co-existing fibromyalgia (FM) may explain this disparity. FM has been characterised by aberrant brain functional connectivity, especially between the Default Mode Network (DMN) and insula. We hypothesised that RA patients reporting the highest 2011 ACR FM survey criteria scores- a continuous measure of FM degree also known as fibromyalgianess (FMness)- would demonstrate functional connectivity abnormalities similar to FM. Methods: RA patients underwent an 11 min functional connectivity MRI brain scan (fcMRI) and a clinical evaluation which included a measure of FMness. Brain networks were isolated from FcMRI data. Individual patient network to whole brain connectivity analyses were then conducted followed by group level regression which correlated the connectivity of each network with FMness. Results were significant on the cluster level with a family wise error (FWE) rate p-value <0.05 derived from an uncorrected voxel level p-value <0.001. Results: 54 patients participated (mean age 54.9years; 75.9{\%} female; mean FMness score 13.3 [range 1-29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r=0.58, p=0.001 FWE) was demonstrated. Conclusions: RA patients who have increased levels of FMness appear to share neurobiological features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients’ symptoms being related to CNS rather than classic inflammatory mechanisms.",
author = "Neil Basu and Kaplan, {Chelsea M.} and Eric Ichesco and Tony Larkin and Harris, {Richard E.} and Alison Murray and Gordon Waiter and Clauw, {Daniel J.}",
note = "Funding: The study recieved support from Pfizer. The funder had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors. Funding Information Pfizer Aptinyx Cerephex ACKNOWLEDGEMENTS: The authors wish to thank all of the patient volunteers. We also thank Mariella D’Allesandro for supporting recruitment and data collection.",
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AU - Kaplan, Chelsea M.

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AU - Murray, Alison

AU - Waiter, Gordon

AU - Clauw, Daniel J.

N1 - Funding: The study recieved support from Pfizer. The funder had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors. Funding Information Pfizer Aptinyx Cerephex ACKNOWLEDGEMENTS: The authors wish to thank all of the patient volunteers. We also thank Mariella D’Allesandro for supporting recruitment and data collection.

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N2 - Objectives: Many rheumatoid arthritis (RA) patients report pain despite excellent control of inflammation with immunotherapies. Variable degrees of co-existing fibromyalgia (FM) may explain this disparity. FM has been characterised by aberrant brain functional connectivity, especially between the Default Mode Network (DMN) and insula. We hypothesised that RA patients reporting the highest 2011 ACR FM survey criteria scores- a continuous measure of FM degree also known as fibromyalgianess (FMness)- would demonstrate functional connectivity abnormalities similar to FM. Methods: RA patients underwent an 11 min functional connectivity MRI brain scan (fcMRI) and a clinical evaluation which included a measure of FMness. Brain networks were isolated from FcMRI data. Individual patient network to whole brain connectivity analyses were then conducted followed by group level regression which correlated the connectivity of each network with FMness. Results were significant on the cluster level with a family wise error (FWE) rate p-value <0.05 derived from an uncorrected voxel level p-value <0.001. Results: 54 patients participated (mean age 54.9years; 75.9% female; mean FMness score 13.3 [range 1-29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r=0.58, p=0.001 FWE) was demonstrated. Conclusions: RA patients who have increased levels of FMness appear to share neurobiological features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients’ symptoms being related to CNS rather than classic inflammatory mechanisms.

AB - Objectives: Many rheumatoid arthritis (RA) patients report pain despite excellent control of inflammation with immunotherapies. Variable degrees of co-existing fibromyalgia (FM) may explain this disparity. FM has been characterised by aberrant brain functional connectivity, especially between the Default Mode Network (DMN) and insula. We hypothesised that RA patients reporting the highest 2011 ACR FM survey criteria scores- a continuous measure of FM degree also known as fibromyalgianess (FMness)- would demonstrate functional connectivity abnormalities similar to FM. Methods: RA patients underwent an 11 min functional connectivity MRI brain scan (fcMRI) and a clinical evaluation which included a measure of FMness. Brain networks were isolated from FcMRI data. Individual patient network to whole brain connectivity analyses were then conducted followed by group level regression which correlated the connectivity of each network with FMness. Results were significant on the cluster level with a family wise error (FWE) rate p-value <0.05 derived from an uncorrected voxel level p-value <0.001. Results: 54 patients participated (mean age 54.9years; 75.9% female; mean FMness score 13.3 [range 1-29]). From the whole brain analyses, a single significant positive correlation between DMN connectivity to the left mid/posterior insula and FMness (r=0.58, p=0.001 FWE) was demonstrated. Conclusions: RA patients who have increased levels of FMness appear to share neurobiological features consistently observed in FM patients. This study is the first to provide neuroimaging evidence that RA is a mixed pain state, with many patients’ symptoms being related to CNS rather than classic inflammatory mechanisms.

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