Basal inflammation and innate immune response in chronic multisite musculoskeletal pain

Ellen Generaal; Nicole Vogelzangs; Gary J Macfarlane; Rinie Geenen; Johannes H Smit; Joost Dekker; Brenda W J H Penninx

doi:10.1016/j.pain.2014.05.007

Basal inflammation and innate immune response in chronic multisite musculoskeletal pain

Ellen Generaal, Nicole Vogelzangs, Gary J Macfarlane, Rinie Geenen, Johannes H Smit, Joost Dekker, Brenda W J H Penninx

Research output: Contribution to journal › Article › peer-review

48 Citations (Scopus)

Abstract

Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain. Data were used on 1632 subjects of the Netherlands Study of Depression and Anxiety. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multisite musculoskeletal pain. Subjects were categorized in a chronic multisite musculoskeletal pain group (n=754) and a control group (n=878). Blood levels of the basal inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were determined. To obtain a measure of the innate immune response, 13 inflammatory markers were assessed after lipopolysaccharide (LPS) stimulation in a subsample (n=707). Subjects with chronic multisite musculoskeletal pain showed elevated levels of basal inflammatory markers compared with controls, but statistical significance was lost after adjustment for lifestyle and disease variables. For some LPS-stimulated inflammatory markers, we did find elevated levels in subjects with chronic multisite musculoskeletal pain both before and after adjustment for covariates. Pain severity was not associated with inflammation within chronic pain subjects. An enhanced innate immune response in chronic multisite musculoskeletal pain may be examined as a potential biomarker for the onset or perpetuation of chronic pain.

Original language	English
Pages (from-to)	1605-1612
Number of pages	8
Journal	Pain
Volume	155
Issue number	8
Early online date	9 May 2014
DOIs	https://doi.org/10.1016/j.pain.2014.05.007
Publication status	Published - Aug 2014

Bibliographical note

Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Acknowledgements
This manuscript is part of the PhD programme investigating neurobiological dysregulation in chronic pain, funded through The European League Against Rheumatism (EULAR). The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organisations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, Netherlands Institute for Health Services Research [NIVEL] and Netherlands Institute of Mental Health and Addiction [Trimbos]). Assaying of basal inflammatory markers was supported by the Neuroscience Campus Amsterdam. Assaying of LPS-stimulated inflammatory markers was supported by Hersenstichting Nederland [2011(1)-134] and Myriad RBM, Austin, TX.

Keywords

immune system
c-reactive protein
cytokines
lipopolysaccharide
innate immune response
chronic pain
central sensitization

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10.1016/j.pain.2014.05.007

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title = "Basal inflammation and innate immune response in chronic multisite musculoskeletal pain",

abstract = "Dysregulation of the immune system may play a role in chronic pain, although study findings are inconsistent. This cross-sectional study examined whether basal inflammatory markers and the innate immune response are associated with the presence and severity of chronic multisite musculoskeletal pain. Data were used on 1632 subjects of the Netherlands Study of Depression and Anxiety. The Chronic Pain Grade questionnaire was used to determine the presence and severity of chronic multisite musculoskeletal pain. Subjects were categorized in a chronic multisite musculoskeletal pain group (n=754) and a control group (n=878). Blood levels of the basal inflammatory markers C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were determined. To obtain a measure of the innate immune response, 13 inflammatory markers were assessed after lipopolysaccharide (LPS) stimulation in a subsample (n=707). Subjects with chronic multisite musculoskeletal pain showed elevated levels of basal inflammatory markers compared with controls, but statistical significance was lost after adjustment for lifestyle and disease variables. For some LPS-stimulated inflammatory markers, we did find elevated levels in subjects with chronic multisite musculoskeletal pain both before and after adjustment for covariates. Pain severity was not associated with inflammation within chronic pain subjects. An enhanced innate immune response in chronic multisite musculoskeletal pain may be examined as a potential biomarker for the onset or perpetuation of chronic pain.",

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author = "Ellen Generaal and Nicole Vogelzangs and Macfarlane, {Gary J} and Rinie Geenen and Smit, {Johannes H} and Joost Dekker and Penninx, {Brenda W J H}",

note = "Copyright {\textcopyright} 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. Acknowledgements This manuscript is part of the PhD programme investigating neurobiological dysregulation in chronic pain, funded through The European League Against Rheumatism (EULAR). The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10-000-1002) and is supported by participating universities and mental health care organisations (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, Netherlands Institute for Health Services Research [NIVEL] and Netherlands Institute of Mental Health and Addiction [Trimbos]). Assaying of basal inflammatory markers was supported by the Neuroscience Campus Amsterdam. Assaying of LPS-stimulated inflammatory markers was supported by Hersenstichting Nederland [2011(1)-134] and Myriad RBM, Austin, TX.",

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AU - Penninx, Brenda W J H

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JO - Pain

JF - Pain

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Basal inflammation and innate immune response in chronic multisite musculoskeletal pain

Abstract

Bibliographical note

Keywords

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