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.

Neck-shoulder pain (NSP) is a highly prevalent musculoskeletal disorder with unclear causes, and effective prevention and treatment require a further understanding of the underlying mechanisms. Aberrant autonomic nervous system (ANS) regulation is a hypothesized causal element in the development and maintenance of chronic muscle pain. The overall aim of this thesis was to investigate possible differences in ANS regulation between chronic NSP and healthy control (CON) groups using both laboratory assessment and ambulatory monitoring in daily life. Four papers are included in this thesis, based on data from three groups with chronic NSP. Autonomic responses to laboratory stressors were assessed using heart rate variability (HRV), blood pressure, trapezius muscle activity and blood flow measurements (Study І) in NSP and CON. Long-term ambulatory monitoring of HRV, physical activity and perceived symptoms were assessed in Studies ІІ and IV to investigate group differences in real-life conditions. Finally, the effects of a ten-week intervention (using individually adjusted HRV biofeedback) to reinstating ANS balance in subjects with chronic NSP were evaluated using self-reported symptoms and health ratings, as well as autonomic regulation testing (i.e., evaluating HRV at rest and in response to stress) (Study ІІІ). The main findings from the four studies demonstrated aberrant ANS regulation in the NSP group compared to CON, which was predominantly characterized by diminished parasympathetic cardiac activity during rest and sleep, and altered sympathetic reactivity to laboratory stressors (Studies І, ІІ and IV). Different patterns in physical activity were observed between the NSP and CON groups, with reduced physical activity during leisure time in the NSP group (Studies ІІ and IV). Physical activity was found to be positively associated with HRV. Positive effects of HRV-biofeedback were found on perceived health, including social function, vitality and bodily pain, and improved HRV (Study ІІІ). In conclusion, imbalanced ANS regulation was demonstrated among persons with chronic NSP at both the systemic and local levels. Diminished parasympathetic activity in NSP was modulated by lower levels of physical activity in leisure time. Interventions targeting ANS functions might benefit persons with chronic NSP.

Prolonged computer work is associated with high rates of neck and shoulder pain symptoms, and as computers have become increasingly more common, it is becoming critical that we develop sustainable interventions targeting this issue. Static muscle contractions for prolonged periods often occur in the neck/shoulder during computer work and may underlie muscle pain development in spite of rather low relative muscle load levels. Causal mechanisms may include a stereotypical recruitment of low threshold motor units (activating type I muscle fibers), characterized by a lack of temporal as well as spatial variation in motor unit recruitment. Based on this theory, although studies have postulated that individuals with chronic neck-shoulder pain will show less variation in muscle activity compared to healthy individuals when engaged in repetitive/monotonous work, this has seldom been verified in empirical studies of actual computer work. Studies have rarely addressed temporal patterns in muscle activation, even though there is a consensus that temporal activation patterns are important for understanding fatigue and maybe even risks of subsequent musculoskeletal disorders. This study applied exposure variation analysis (EVA) to study differences in temporal patterns of trapezius muscle activity as individuals with and without pain performed computer work. The aims of this study were to: Assess the reliability of EVA to measure variation in trapezius muscle activity in healthy individuals during the performance of computer work; Determine the extent to which healthy subjects differ from those with chronic pain in trapezius muscle activity patterns during computer work, measured using EVA. Thirteen touch-typing, right-handed participants were recruited in this study (8 healthy; 5 chronic pain). The participants were asked to complete three 10-minute computer tasks (TYPE, CLICK and FORM) in two pacing conditions (self-paced, control-paced), with the healthy group completing two sessions and the pain group completing one. Activation of the upper trapezius muscle was measured using surface electromyography (EMG). EMG data were organized into 5x5 EVA matrices with five amplitude classes (0-6.67, 6.67-20, 20-46.67, 46.67-100, >100% Reference Voluntary Exertion) and five duration classes (0- 1, 1-3, 3-7, 7-15, >15 seconds). EVA marginal distributions (along both amplitude and duration classes) for each EVA class, as well as summary measures (mean and SD) of the marginal sums along each axis were computed. Finally, “resultant” mean and SD across all EVA cells were computed. The reliability in EVA indices was estimated using intra-class correlation coefficients (ICC), coefficient of variation (CV) and standard error of measurement (SEM), computed from repeated measurements of healthy individuals (aim 1), and EVA indices were compared between groups (aim 2). Reliability of EVA amplitude marginal sums ranged from moderate to high in the self-paced condition and low to moderate in the control-paced condition. The duration marginal sums were moderate in the self-paced condition and moderate to high in the control-paced condition. The summary measures (means and SDs) were moderate to high in both the self-paced and control-paced condition. Group comparisons revealed that individuals with chronic pain spent longer durations of work time in higher EVA duration categories, exhibited larger means along the amplitude, duration and in the resultant, and higher EVA SD in the amplitude and duration axes as compared to the healthy group. To our knowledge, this is the first study to report on the reliability of EVA applied specifically to computer work. Furthermore, EVA was used to assess differences in muscle activation patterns as individuals with and without chronic pain engaged in computer work. Individuals in the pain group seemed to exhibit prolonged sustained activation of the trapezius muscle to a significantly greater extent than controls, even though they did not experience pain during the performance of the computer tasks (as obtained through self-reports). Thus, these altered muscle recruitment patterns observed in the pain subjects, even in the absence of task-based pain/discomfort, are suggestive of chronic motor control changes occurring in adaptation to pain, and may have implications for the etiology of neck and upper-limb musculoskeletal disorders. / Master of Science / This study aims to assess the reliability of exposure variation analysis (EVA) to measure variation in trapezius muscle activity in healthy individuals during the performance of computer work, and to determine the extent to which healthy subjects differ from those with chronic pain in trapezius muscle activity patterns during computer work, measured using EVA. Muscle activation was recorded for eight healthy individual and five suffering from chronic neck-shoulder pain. The data were then categorized into amplitude and continuous time categories, and summary measures of resulting distributions were calculated. These measures were used to assess the reliability of participant responses to computer work of healthy individuals, as well as quantify differences between those with and without chronic pain. We found that individuals with pain activated their neck-shoulder muscles for longer continuous durations than healthy individuals, thus showing an inability to relax their muscles when performing work.