| 1. |
- Barbe, MF, et al.
(författare)
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Sickness behaviors (reduced social interaction and pain behaviors) are linked to inflammatory mechanisms in a rat model of work-related musculoskeletal disorders
- 2016
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Ingår i: Proceedings of the Human Factors and Ergonomics Society Annual Meeting. - : Sage Publications. - 1541-9312 .- 2169-5067 .- 1071-1813. ; 60:1, s. 975-979
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Tidskriftsartikel (refereegranskat)abstract
- We sought to determine if sickness behaviors (decreased social interaction and pain) are induced in a rat model of work-related overuse and effectiveness of anti-inflammatory treatments. Rats first trained to learn a high force reaching task (15 min/week day for 6 wks), with subsets treated prophylactically with ibuprofen or anti-TNFalpha. Others performed a high repetition high force (HRHF) task for 6 or 12 weeks (2 hrs/day, 3 days/wk) untreated, or with ibuprofen, anti-TNFalpha or rest treatments beginning task week 5. Untreated HRHF rats had increased IL-1beta, IL-6 and TNFalpha in serum and brain, increased Substance P in spinal cord, decreased social interaction and increased forepaw allodynia. Secondary antiinflammatory treatments attenuated social interaction and brain changes, but not allodynia or spinal cord changes; rest provided partial attenuation. Prophylactic treatments prevented all changes. Thus, inflammatory mechanisms mediate the development of sickness behaviors induced by work-related overuse, but not maintenance of allodynia.
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| 2. |
- Hadrévi, Jenny, 1977-
(författare)
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Applying proteomics and metabolomics for studying human skeletal muscle with a focus on chronic trapezius myalgia
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 3. |
- Hadrevi, Jenny
(författare)
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Ca 2+ regulatory proteins of muscle contraction : a possible marker of chronic muscle myalgia
- 2014
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Konferensbidrag (refereegranskat)abstract
- Aim of Investigation: Work related illnesses are one of the main reasons for sick-leave in the western world. One of the most common is pain and discomfort in the neck-shoulder region affecting the trapezius muscle, trapezius myalgia (TM). Patients suffering from work related chronic trapezius myalgia experience muscle stiffness, weakness and tension. The biochemical mechanisms behind these sensations are not yet known. Recent proteomic screening results indicate an increased abundance of the calcium regulatory fast myosin light chains in myalgic muscle suggesting an altered contractibility in the myalgic trapezius. To characterize a general increase of Ca2+ in the myalgic muscle the expression level of sarco/endoplasmic reticulum Ca2+-ATPase, (SERCA-1) was analyzed. The aim of this study was to compare the level of Ca2+ regulated proteins in cleaners with trapezius myalgia (TM) and cleaners without trapezius myalgia (CON) and to verify a possible difference in phosphorylation of the contractile regulatory myosin light chains.Methods: Two-dimensional gel electrophoresis was used to separate proteins of interest. The proteomic correlation pattern of the myosin light chain proteins and the differences between healthy and myalgic muscle were investigated using a multivariate Partial Least Square Discriminant Analysis (PLS-DA). Phosphorylations of the fast regulatory myosin light chains were analyzed using serine and tyrosin antibodies. The characterization of myosin isoforms was performed using advanced Orbitrap LC-MS/MS. The expression level of SERCA-1 was analyzed in muscle biopsies from 11 professional cleaners with TM and 11 CON using Simple western size assay (Peggy, Protein simple, CA, US)Results: The detected systematic differences between myosin light chain proteins showed according to the PLS-DA analysis that the fast regulatory light chains were generally more abundant in the MYA group. Ten protein spots were identified as different myosin light chains isoforms according to the amino acid sequencing. Phosphorylated serine was detected in 6 of the isoforms, though there were no differences in amount of phosphorylation between spots. The expression level of Serca-1 was significantly (p = 0.017) higher in TM subjects compared to the CON.Conclusions: There is a higher abundance of fast contracting calcium regulatory myosin light chains in muscle experiencing chronic myalgia. This increased abundance of the regulatory fast myosin light chains supports the previously presented results showing an altered contractibility of the myalgic trapezius muscle. Our results show no difference in phosphorylation between the different spots contradictory to previously published results; suggesting phosphorylation of the protein being the reason for the separation of spots on the two dimensional gels. Instead our results show the spots to have different amino acid sequences. The actual function of the detected myosin light chain proteins remains to be elucidated. The increased abundance of fast contracting regulatory light chains together with the significantly increased abundance of Serca-1 proteins in the MYA muscle supports a higher abundance of Ca2+ in the myalgic muscle. The increased abundance of Serca-1 might be an indication of an adaptation due to peripheral sensitization or increased neuronal signaling altering the contrability of the muscle. Acknowledgments: Supported by Postdoctoral Grant from Swedish Research Council for Health, Working Life and Welfare (Forte) 2013-1259 and Medical Research Council of Southeast Sweden (FORSS-159031, LIO-35923, SC-2013-00395-36).
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| 4. |
- Hadrevi, Jenny, 1977-, et al.
(författare)
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Calcium Fluxes in Work-Related Muscle Disorder : Implications from a Rat Model
- 2019
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Ingår i: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2019
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Ca2+ regulatory excitation-contraction coupling properties are key topics of interest in the development of work-related muscle myalgia and may constitute an underlying cause of muscle pain and loss of force generating capacity.Method: A well-established rat model of high repetition high force (HRHF) work was used to investigate if such exposure leads to an increase in cytosolic Ca2+ concentration ([Ca2+]i) and changes in sarcoplasmic reticulum (SR) vesicle Ca2+ uptake and release rates.Result: Six weeks exposure of rats to HRHF increased indicators of fatigue, pain behaviors, and [Ca2+]i, the latter implied by around 50–100% increases in pCam, as well as in the Ca2+ handling proteins RyR1 and Casq1 accompanied by an ∼10% increased SR Ca2+ uptake rate in extensor and flexor muscles compared to those of control rats. This demonstrated a work-related altered myocellular Ca2+ regulation, SR Ca2+ handling, and SR protein expression.Discussion: These disturbances may mirror intracellular changes in early stages of human work-related myalgic muscle. Increased uptake of Ca2+ into the SR may reflect an early adaptation to avoid a sustained detrimental increase in [Ca2+]i similar to the previous findings of deteriorated Ca2+ regulation and impaired function in fatigued human muscle.
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| 5. |
- Hadrévi, Jenny, 1977-, et al.
(författare)
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Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study
- 2013
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Ingår i: European Journal of Applied Physiology. - : Springer Verlag (Germany). - 1439-6319 .- 1439-6327. ; 113:12, s. 2977-2989
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Tidskriftsartikel (refereegranskat)abstract
- 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. less thanbrgreater than less thanbrgreater thanMicrodialysate 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. less thanbrgreater than less thanbrgreater thanA 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. less thanbrgreater than less thanbrgreater thanThis study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.
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| 6. |
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| 7. |
- Hadrévi, Jenny, et al.
(författare)
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Dietary Fiber Intake among Normal-Weight and Overweight Female Health Care Workers : An Exploratory Nested Case-Control Study within FINALE-Health
- 2017
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Ingår i: Journal of Nutrition and Metabolism. - : Hindawi Publishing Corporation. - 2090-0724 .- 2090-0732.
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic factors affect choice of diet, that is, dietary fiber intake. Underreporting of food consumption in diet surveys has been reported higher in low-income, low-education groups compared to high-income, high-education groups. This paper examines in a socioeconomic homogenous low-income low-education group of females the relation between dietary fiber intake and overweight and scrutinizes if the level of underreporting is equally large in normal-weight and overweight groups. Thirty-four female health care workers classified as either normal-weight () or obese () based on BMI, fat percentage, and waist circumference participated. A detailed food-diary was used to record their dietary intake in 9 days. Average dietary fiber intake in the normal-weight group was 2.73 +/− 0.65 g/MJ, while it was 2.15 +/− 0.64 g/MJ for the women in the obese group. In both groups, the overall food intake was underreported. In spite of a significantly lower dietary fiber intake in the obese group, the present population of women working within health care all showed an overall low dietary fiber intake and a general underreporting of food intake. These results indicate a clear need for dietary advice especially on fiber intake to increase general health and decrease weight.
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| 8. |
- Hadrevi, Jenny, et al.
(författare)
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Evaluation of trapezius using proteomic methods
- 2007
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Ingår i: Sixth International Scientific Conference on Prevention of Work-Related Musculoskeletal Disorders. ; , s. 274-
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Konferensbidrag (refereegranskat)
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| 9. |
- Hadrevi, Jenny
(författare)
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Human Skeletal Muscle : a basic proteomic approach
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The trapezius is a muscle of clinical interest due to its susceptibility to chronic work related musculoslteletal disorders. The mechanisms underlying these conditions are not fully understood. A comprehensive and comparative biochemical characterization of the trapezius muscle may reveal particular individual traits that make it more susceptible to chronic work related musculoskeletal disorders. We have examined the suitability and outcome of a proteomic method, two-dimensional difference gel electrophoresis (2D-DIGE), in the analysis of human skeletal muscle. This method allows a simultaneous comparison of large numbers of proteins within a limited pH and molecular weight range. A protocol using the 2D-DIGE method was adapted to human muscle and its repeatability was tested on human vastus lateralis muscle samples from one healthy male donor. The vastus lateralis is the most well studied muscle in the human body and was therefore used as the gold standard. The method was validated using western blot technique. Subsequently, a comparative 2D-DIGE analysis using the validated protocol was conducted on vastus lateralis and trapezius muscle biopsies from five healthy male subjects. Proteins were identified using matrix assisted laser desorption ionisation time of flight (MALDI-TOF) mass spectrometry and immunohistochemistry was performed on serial sections to confirm the findings. The 2D-DIGE method proved to be a good screening tool to further detect biochemical differences between muscles. The comparative study between the trapezius and vastus lateralis demonstrated significant differences in 25 important metabolic and structural proteins. In particular, it showed differences in proteins related to oxidative stress, which may be of specific importance for the susceptibility of the trapezius muscle to work related musculoskeletal disorders. These results provide a baseline for future studies on the trapezius muscle and puts further emphasis on the differences between different types of skeletal muscle.
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| 10. |
- Hadrévi, Jenny, 1977-, et al.
(författare)
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Multivariate Modeling of Proteins Related to Trapezius Myalgia, a Comparative Study of Female Cleaners with or without Pain
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:9, s. e73285-
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of chronic trapezius myalgia is high in women with high exposure to awkward working positions, repetitive movements and movements with high precision demands. The mechanisms behind chronic trapezius myalgia are not fully understood. The purpose of this study was to explore the differences in protein content between healthy and myalgic trapezius muscle using proteomics. Muscle biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain free female cleaners were obtained from the descending part of the trapezius. Proteins were separated with two-dimensional differential gel electrophoresis (2D-DIGE) and selected proteins were identified with mass spectrometry. In order to discriminate the two groups, quantified proteins were fitted to a multivariate analysis: partial least square discriminate analysis. The model separated 28 unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to the contractile apparatus, the cytoskeleton and to acute response proteins. The results suggest altered metabolism, a higher abundance of proteins related to inflammation in myalgic cleaners compared to healthy, and a possible alteration of the contractile apparatus. This explorative proteomic screening of proteins related to chronic pain in the trapezius muscle provides new important aspects of the pathophysiology behind chronic trapezius myalgia.
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