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Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. (Anatomi)
Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden.
Rehabilitation Medicine, Department of Medicine and Health Sciences (IMH), Faculty of Health Sciences, Linköping University and Pain and Rehabilitation Centre, County Council of Östergötland, SE 581 85 Linköping, Sweden; Institute of Stress Medicine, Carl Skottsbergs gata 22B, SE 41319 Gothenburg, Sweden.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2013 (English)In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 113, no 12, 2977-2989 p.Article in journal (Other academic) Published
Abstract [en]

The mechanisms behind trapezius myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle.

Microdialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography-mass spectrometry (GC-MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann-Whitney U test of group difference in individual metabolites was also performed.

A large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l-leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta-d-glucopyranose was significantly less abundant in the myalgic muscle.

This study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.

Place, publisher, year, edition, pages
Springer, 2013. Vol. 113, no 12, 2977-2989 p.
Keyword [en]
Metabolomics, trapezius myalgia, microdialysis, repetitive work, GC-MS, metabolites
National Category
Other Basic Medicine
Research subject
Human Anatomy
URN: urn:nbn:se:umu:diva-61396DOI: 10.1007/s00421-013-2716-6OAI: diva2:567349
Swedish Research Council, K2011-69X-21874-01-6Forte, Swedish Research Council for Health, Working Life and Welfare, 2009-1761, 2010-0913

Originally published in thesis in manuscript form.

Available from: 2012-11-12 Created: 2012-11-12 Last updated: 2013-12-18Bibliographically approved
In thesis
1. Applying proteomics and metabolomics for studying human skeletal muscle with a focus on chronic trapezius myalgia
Open this publication in new window or tab >>Applying proteomics and metabolomics for studying human skeletal muscle with a focus on chronic trapezius myalgia
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[en]
Tillämpning av proteomiska och metabolomiska metoder på human skelettmuskel med inriktning mot kronisk trapezius myalgi
Abstract [en]

Work related musculoskeletal disorders are the dominating causes of reported ill-health in industrialized countries. These chronic pain conditions are one of the most costly public health problems in Europe and North America. When work related musculoskeletal disorders are considered to be of muscular origin and the trapezius muscle is affected, the common appellation is trapezius myalgia. Since little is known about the genesis or how it is maintained, it is of great importance to better understand the pathophysiology of trapezius myalgia; doing so will better enable recommendations for prevention, treatment and rehabilitation. Several hypotheses have been presented based on biochemical alterations in the muscle, suggesting increased signaling of inflammatory substances and altered metabolism. Previous research has not been able to present the comprehensive picture of the muscle in pain. Thus there is a demand for more comprehensive research regarding the biochemical milleu of the chronic trapezius muscle.

Proteomic and metabolomic methods allow non-targeted simultaneous analyses of a large number of proteins and metabolites. The main emphasis in this thesis is on a proteomic method, two-dimensional differential gel electrophoresis (2D-DIGE). The method is validated to human skeletal muscle biopsy research with laboratory specific settings. In the baseline study, there were 14 metabolic, contractile, structural and regulatory proteins that differed significantly in abundance when trapezius and vastus lateralis muscles were compared. Using the validated 2D-DIGE method and the baseline study, a comparison between healthy and myalgic muscles was made. Biopsies from female cleaners with and without myalgia were compared to obtain results from women with the same type of work exposure. In the multivariate model, 28 identified unique proteins separated healthy and myalgic muscle and were grouped according to function: metabolic (n=10), contractile (n=9), regulatory (n=3), structural (n=4), and other (n=2). Finally, a second screening method, metabolomics, was introduced to analyze differences in metabolite content as a complement to and verification of the proteomic results. Gas chromatography-mass spectrometry (GC-MS) was performed on muscle interstitial fluid samples obtained with microdialysis, and differences in the abundance of extracellular metabolites were revealed.

 The 2D-DIGE method is a reliable method to analyze human skeletal muscle. The outcomes of the proteomic analyses were dependant on the statistical approach. Systematic differences in protein and metabolite content were detected using a multivariate approach. Univariate analyses were used to analyze individual proteins for their significance. The significant proteins in the baseline study were predominately related to muscle fiber type which correlated with the differences in fiber type content between trapezius and vastus lateralis. The proteomic and metabolomics studies where myalgic and healthy muscles were compared provide us with new clues and new aspects regarding the pathophysiology of the myalgic muscle.

Technically advanced methods employed in the thesis enabled an explorative screening of proteins of relevance for the pathophysiology of the myalgic muscle. The results of these analyses may contribute to the formulation of future hypothesis that need to be further evaluated.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2012. 60 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1533
Trapezius myalgia, proteomics, 2D-DIGE, metabolomics, microdialysate, biopsies
National Category
Other Basic Medicine
Research subject
Human Anatomy
urn:nbn:se:umu:diva-61399 (URN)978-91-7459-515-4 (ISBN)
Public defence
2012-12-06, BiA 201, Biologihuset, Umeå Universitet, Umeå, 09:00 (English)
Available from: 2012-11-15 Created: 2012-11-12 Last updated: 2012-11-15Bibliographically approved

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