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      Specific proteins of the trapezius muscle correlate with pain intensity and sensitivity – an explorative multivariate proteomic study of the trapezius muscle in women with chronic widespread pain

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          Abstract

          Chronic widespread pain (CWP) including fibromyalgia syndrome (FMS) has a high prevalence and is associated with prominent negative consequences. CWP/FMS exhibits morphological and functional alterations in the central nervous system. The importance of peripheral factors for maintaining the central alterations are under debate. In this study, the proteins from biopsies of the trapezius muscle from 18 female CWP/FMS patients and 19 healthy female controls were analyzed. Pain intensity and pressure pain thresholds (PPT) over the trapezius muscles were registered. Twelve proteins representing five different groups of proteins were important regressors of pain intensity in CWP/FMS ( R 2=0.99; P<0.001). In the regression of PPT in CWP/FMS, it was found that 16 proteins representing six groups of proteins were significant regressors ( R 2=0.95, P<0.05). Many of the important proteins were stress and inflammation proteins, enzymes involved in metabolic pathways, and proteins associated with muscle damage, myopathies, and muscle recovery. The altered expression of these proteins may reflect both direct and indirect nociceptive/inflammatory processes as well as secondary changes. The relative importance of the identified proteins and central alterations in CWP need to be investigated in future research. Data from this and the previous study concerning the same cohorts give support to the suggestion that peripheral factors are of importance for maintaining pain aspects in CWP/FMS.

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          Most cited references 61

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          Biochemical markers of muscular damage.

          Muscle tissue may be damaged following intense prolonged training as a consequence of both metabolic and mechanical factors. Serum levels of skeletal muscle enzymes or proteins are markers of the functional status of muscle tissue, and vary widely in both pathological and physiological conditions. Creatine kinase, lactate dehydrogenase, aldolase, myoglobin, troponin, aspartate aminotransferase, and carbonic anhydrase CAIII are the most useful serum markers of muscle injury, but apoptosis in muscle tissues subsequent to strenuous exercise may be also triggered by increased oxidative stress. Therefore, total antioxidant status can be used to evaluate the level of stress in muscle by other markers, such as thiobarbituric acid-reactive substances, malondialdehyde, sulfhydril groups, reduced glutathione, oxidized glutathione, superoxide dismutase, catalase and others. As the various markers provide a composite picture of muscle status, we recommend using more than one to provide a better estimation of muscle stress.
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            Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation and clinical applications.

             U Proske,  D Morgan (2001)
            In eccentric exercise the contracting muscle is forcibly lengthened; in concentric exercise it shortens. While concentric contractions initiate movements, eccentric contractions slow or stop them. A unique feature of eccentric exercise is that untrained subjects become stiff and sore the day afterwards because of damage to muscle fibres. This review considers two possible initial events as responsible for the subsequent damage, damage to the excitation-contraction coupling system and disruption at the level of the sarcomeres. Other changes seen after eccentric exercise, a fall in active tension, shift in optimum length for active tension, and rise in passive tension, are seen, on balance, to favour sarcomere disruption as the starting point for the damage. As well as damage to muscle fibres there is evidence of disturbance of muscle sense organs and of proprioception. A second period of exercise, a week after the first, produces much less damage. This is the result of an adaptation process. One proposed mechanism for the adaptation is an increase in sarcomere number in muscle fibres. This leads to a secondary shift in the muscle's optimum length for active tension. The ability of muscle to rapidly adapt following the damage from eccentric exercise raises the possibility of clinical applications of mild eccentric exercise, such as for protecting a muscle against more major injuries.
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              Trials and tribulations of 'omics data analysis: assessing quality of SIMCA-based multivariate models using examples from pulmonary medicine.

              Respiratory diseases are multifactorial heterogeneous diseases that have proved recalcitrant to understanding using focused molecular techniques. This trend has led to the rise of 'omics approaches (e.g., transcriptomics, proteomics) and subsequent acquisition of large-scale datasets consisting of multiple variables. In 'omics technology-based investigations, discrepancies between the number of variables analyzed (e.g., mRNA, proteins, metabolites) and the number of study subjects constitutes a major statistical challenge. The application of traditional univariate statistical methods (e.g., t-test) to these "short-and-wide" datasets may result in high numbers of false positives, while the predominant approach of p-value correction to account for these high false positive rates (e.g., FDR, Bonferroni) are associated with significant losses in statistical power. In other words, the benefit in decreased false positives must be counterbalanced with a concomitant loss in true positives. As an alternative, multivariate statistical analysis (MVA) is increasingly being employed to cope with 'omics-based data structures. When properly applied, MVA approaches can be powerful tools for integration and interpretation of complex 'omics-based datasets towards the goal of identifying biomarkers and/or subphenotypes. However, MVA methods are also prone to over-interpretation and misuse. A common software used in biomedical research to perform MVA-based analyses is the SIMCA package, which includes multiple MVA methods. In this opinion piece, we propose guidelines for minimum reporting standards for a SIMCA-based workflow, in terms of data preprocessing (e.g., normalization, scaling) and model statistics (number of components, R2, Q2, and CV-ANOVA p-value). Examples of these applications in recent COPD and asthma studies are provided. It is expected that readers will gain an increased understanding of the power and utility of MVA methods for applications in biomedical research.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                1178-7090
                2016
                02 June 2016
                : 9
                : 345-356
                Affiliations
                Pain and Rehabilitation Centre, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
                Author notes
                Correspondence: Patrik Olausson, Pain and Rehabilitation Centre, Department of Medical and Health Sciences, Linköping University, SE 581 85 Linköping, Sweden, Tel +46 10 103 4155, Email patrik.olausson@ 123456liu.se
                Article
                jpr-9-345
                10.2147/JPR.S102275
                4898258
                27330327
                © 2016 Olausson et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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