Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content

ObjectivesThis explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associ...

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Main Authors: Björn Gerdle, Olof Dahlqvist Leinhard, Eva Lund, Peter Lundberg, Mikael Fredrik Forsgren, Bijar Ghafouri
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Pain Research
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fpain.2024.1288024/full
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author Björn Gerdle
Björn Gerdle
Olof Dahlqvist Leinhard
Olof Dahlqvist Leinhard
Olof Dahlqvist Leinhard
Eva Lund
Peter Lundberg
Peter Lundberg
Mikael Fredrik Forsgren
Mikael Fredrik Forsgren
Mikael Fredrik Forsgren
Bijar Ghafouri
author_facet Björn Gerdle
Björn Gerdle
Olof Dahlqvist Leinhard
Olof Dahlqvist Leinhard
Olof Dahlqvist Leinhard
Eva Lund
Peter Lundberg
Peter Lundberg
Mikael Fredrik Forsgren
Mikael Fredrik Forsgren
Mikael Fredrik Forsgren
Bijar Ghafouri
author_sort Björn Gerdle
collection DOAJ
description ObjectivesThis explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls.MethodsHere, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)—i.e., muscle volume, fat content and infiltration—were also performed.ResultsAfter standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant.DiscussionPeripheral factors were important for group differentiation between FM and controls. In saliva (but not plasma), cytokines and chemokines were significantly associated with group membership as saliva compounds were increased in FM. The importance of peripheral factors for group differentiation increased when muscle compounds and body composition variables were also included. Plasma proteins were important for pain intensity and sensitivity. Cytokines and chemokines mainly from plasma were also significantly and positively associated with a fat infiltration and content index.ConclusionOur findings of associations between cytokines and chemokines and fat infiltration and content in different tissues confirm that inflammation and immune factors are secreted from adipose tissue. FM is clearly characterized by complex interactions between peripheral tissues and the peripheral and central nervous systems, including nociceptive, immune, and neuroendocrine processes.
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spelling doaj.art-9ae5101e6a9e49aab918e1d9c53b0a662024-01-18T04:45:00ZengFrontiers Media S.A.Frontiers in Pain Research2673-561X2024-01-01510.3389/fpain.2024.12880241288024Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and contentBjörn Gerdle0Björn Gerdle1Olof Dahlqvist Leinhard2Olof Dahlqvist Leinhard3Olof Dahlqvist Leinhard4Eva Lund5Peter Lundberg6Peter Lundberg7Mikael Fredrik Forsgren8Mikael Fredrik Forsgren9Mikael Fredrik Forsgren10Bijar Ghafouri11Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SwedenCenter for Medical Image Science and Visualization (CMIV), Linköping, SwedenCenter for Medical Image Science and Visualization (CMIV), Linköping, SwedenRadiation Physics, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SwedenAMRA Medical AB, Linköping, SwedenRadiation Physics, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SwedenCenter for Medical Image Science and Visualization (CMIV), Linköping, SwedenDepartment of Radiation Physics, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SwedenCenter for Medical Image Science and Visualization (CMIV), Linköping, SwedenRadiation Physics, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SwedenAMRA Medical AB, Linköping, SwedenPain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, SwedenObjectivesThis explorative study analyses interrelationships between peripheral compounds in saliva, plasma, and muscles together with body composition variables in healthy subjects and in fibromyalgia patients (FM). There is a need to better understand the extent cytokines and chemokines are associated with body composition and which cytokines and chemokines differentiate FM from healthy controls.MethodsHere, 32 female FM patients and 30 age-matched female healthy controls underwent a clinical examination that included blood sample, saliva samples, and pain threshold tests. In addition, the subjects completed a health questionnaire. From these blood and saliva samples, a panel of 68 mainly cytokines and chemokines were determined. Microdialysis of trapezius and erector spinae muscles, phosphorus-31 magnetic resonance spectroscopy of erector spinae muscle, and whole-body magnetic resonance imaging for determination of body composition (BC)—i.e., muscle volume, fat content and infiltration—were also performed.ResultsAfter standardizing BC measurements to remove the confounding effect of Body Mass Index, fat infiltration and content are generally increased, and fat-free muscle volume is decreased in FM. Mainly saliva proteins differentiated FM from controls. When including all investigated compounds and BC variables, fat infiltration and content variables were most important, followed by muscle compounds and cytokines and chemokines from saliva and plasma. Various plasma proteins correlated positively with pain intensity in FM and negatively with pain thresholds in all subjects taken together. A mix of increased plasma cytokines and chemokines correlated with an index covering fat infiltration and content in different tissues. When muscle compounds were included in the analysis, several of these were identified as the most important regressors, although many plasma and saliva proteins remained significant.DiscussionPeripheral factors were important for group differentiation between FM and controls. In saliva (but not plasma), cytokines and chemokines were significantly associated with group membership as saliva compounds were increased in FM. The importance of peripheral factors for group differentiation increased when muscle compounds and body composition variables were also included. Plasma proteins were important for pain intensity and sensitivity. Cytokines and chemokines mainly from plasma were also significantly and positively associated with a fat infiltration and content index.ConclusionOur findings of associations between cytokines and chemokines and fat infiltration and content in different tissues confirm that inflammation and immune factors are secreted from adipose tissue. FM is clearly characterized by complex interactions between peripheral tissues and the peripheral and central nervous systems, including nociceptive, immune, and neuroendocrine processes.https://www.frontiersin.org/articles/10.3389/fpain.2024.1288024/fulladiposebiomarkerbody compositionfatfibromyalgiainflammation
spellingShingle Björn Gerdle
Björn Gerdle
Olof Dahlqvist Leinhard
Olof Dahlqvist Leinhard
Olof Dahlqvist Leinhard
Eva Lund
Peter Lundberg
Peter Lundberg
Mikael Fredrik Forsgren
Mikael Fredrik Forsgren
Mikael Fredrik Forsgren
Bijar Ghafouri
Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
Frontiers in Pain Research
adipose
biomarker
body composition
fat
fibromyalgia
inflammation
title Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
title_full Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
title_fullStr Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
title_full_unstemmed Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
title_short Pain and the biochemistry of fibromyalgia: patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain, fat infiltration and content
title_sort pain and the biochemistry of fibromyalgia patterns of peripheral cytokines and chemokines contribute to the differentiation between fibromyalgia and controls and are associated with pain fat infiltration and content
topic adipose
biomarker
body composition
fat
fibromyalgia
inflammation
url https://www.frontiersin.org/articles/10.3389/fpain.2024.1288024/full
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