Project description:Chronic widespread pain (CWP) has a high prevalence in the population and is associated with prominent negative individual and societal consequences. There is no clear consensus concerning the etiology behind CWP although alterations in the central processing of nociception maintained by peripheral nociceptive input has been suggested. Here, we use proteomics to study protein changes in trapezius muscle from 18 female patients diagnosed with CWP compared to 19 healthy female subjects. The 2-dimensional gel electrophoresis (2-DE) in combination with multivariate statistical analyses revealed 17 proteins to be differently expressed between the two groups. Proteins were identified by mass spectrometry. Many of the proteins are important enzymes in metabolic pathways like the glycolysis and gluconeogenesis. Other proteins are associated with muscle damage, muscle recovery, stress and inflammation. The altered expressed levels of these proteins suggest abnormalities and metabolic changes in the myalgic trapezius muscle in CWP. Taken together, this study gives further support that peripheral factors may be of importance in maintaining CWP.
Project description:BackgroundMicrodialysis (MD) of the trapezius muscle has been an attractive technique to investigating small molecules and metabolites in chronic musculoskeletal pain in human. Large biomolecules such as proteins also cross the dialysis membrane of the catheters. In this study we have applied in vivo MD in combination with two dimensional gel electrophoresis (2-DE) and mass spectrometry to identify proteins in the extracellular fluid of the trapezius muscle.Materials and methodsDialysate from women with chronic trapezius myalgia (TM; n?=?37), women with chronic wide spread pain (CWP; n?=?18) and healthy controls (CON; n?=?22) was collected from the trapezius muscle using a catheter with a cut-off point of 100 kDa. Proteins were separated by two-dimensional gel electrophoresis and visualized by silver staining. Detected proteins were identified by nano liquid chromatography in combination with tandem mass spectrometry.ResultsNinety-seven protein spots were identified from the interstitial fluid of the trapezius muscle; 48 proteins in TM and 30 proteins in CWP had concentrations at least two-fold higher or lower than in CON. The identified proteins pertain to several functional classes, e.g., proteins involved in inflammatory responses. Several of the identified proteins are known to be involved in processes of pain such as: creatine kinase, nerve growth factor, carbonic anhydrase, myoglobin, fatty acid binding protein and actin aortic smooth muscle.ConclusionsIn this study, by using in vivo microdialysis in combination with proteomics a large number of proteins in muscle interstitium have been identified. Several of the identified proteins were at least two-fold higher or lower in chronic pain patients. The applied techniques open up for the possibility of investigating protein changes associated with nociceptive processes of chronic myalgia.
Project description:Microdialysis (MD) has been shown to be a promising technique for sampling of biomarkers. Implantation of MD probe causes an acute tissue trauma and provokes innate response cascades. In order to normalize tissue a two hours equilibration period for analysis of small molecules has been reported previously. However, how the proteome profile changes due to this acute trauma has yet to be fully understood. To characterize the early proteome events induced by this trauma we compared proteome in muscle dialysate collected during the equilibration period with two hours later in "post-trauma". Samples were collected from healthy females using a 100 kDa MW cut off membrane and analyzed by high sensitive liquid chromatography tandem mass spectrometry. Proteins involved in stress response, immune system processes, inflammatory responses and nociception from extracellular and intracellular fluid spaces were identified. Sixteen proteins were found to be differentially abundant in samples collected during first two hours in comparison to "post-trauma". Our data suggests that microdialysis in combination with mass spectrometry may provide potentially new insights into the interstitial proteome of trapezius muscle, yet should be further adjusted for biomarker discovery and diagnostics. Moreover, MD proteome alterations in response to catheter injury may reflect individual innate reactivity.
Project description:PURPOSE:Shear-wave elastography has been recognized a useful tool for quantifying muscle stiffness, commonly reported as shear modulus, however the reports on reliability are often limited to test-retest correlations. In this study, we explored the reliability of shear-wave elastography for assessment of the trapezius muscle stiffness and its relationship with low-level muscle activity. METHODS:Twenty participants were included in a two-session experiment. Measurements of shear modulus and muscle activity were performed at rest and during low-level activity, induced by shoulder abduction without additional external resistance. RESULTS:Good to excellent intra-session repeatability (ICC > 0.80) and moderate inter-rater and inter-session reproducibility (ICC = 0.66-0.74) were observed. Typical errors were acceptable (7.6% of the mean value) only for intra-session measurements in resting conditions, but not acceptable for all conditions with low-level muscle activity (10.2-16.6% of the mean value). Inverse relationships between shear modulus and muscle activity at 40° and 60° of shoulder abduction (r = -0.53 and -0.57) were observed on a group level. We also found higher shear modulus in males compared to females, for the parallel probe position compared to the perpendicular position (in relation to muscle fiber orientation), and for the dominant side of the body compared to the non-dominant side. CONCLUSIONS:This study showed an inverse relationship between muscle activity in low-level range and shear modulus on a group level, suggesting inherent passive stiffness could account for a larger portion of the variance (compared to muscle activity) in shear modulus when the muscle activity is low. Our results imply that shear-wave elastography can be used in research exploring muscle stiffness, however, caution is needed since only intra-session examination in resting conditions showed acceptable within-participant typical errors. The secondary analyses of the study showed higher shear modulus for males, for the non-dominant side of the body and for the parallel orientation of the ultrasound probe.
Project description:Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3?minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies.
Project description:In this study, we tested the hypotheses that unaccustomed eccentric exercise (ECC) would reduce the elastic modulus and dynamic stiffness of the upper trapezius muscle and that these changes would correlate with increases in muscle thickness, reflecting muscle edema. Shear wave elastography was used to measure elastic modulus, dynamic stiffness was assessed using myotonometry, and muscle thickness was measured using ultrasonography. All measurements were performed at four locations over the upper trapezius before and 24 h after a single bout of ECC. Fourteen healthy participants (11 males and 3 females; 23.2 ± 3.0 years; height 175.1 ± 10.4 cm; body mass 73.8 ± 11.3 kg) took part in the study. Overall, ECC resulted in decreased elastic modulus (from 45.8 ± 1.6 to 39.4 ± 1.2 kPa, p < 0.01) and dynamic muscle stiffness (from 369.0 ± 7.3 to 302.6 ± 6.0 N/m, p < 0.01). Additionally, ECC resulted in increased muscle thickness (from 6.9 ± 0.4 to 7.3 ± 0.4 mm, p < 0.01). Spatial changes (across the four locations) were found for elastic modulus, stiffness and thickness. No significant correlations were found between changes in measures of muscle stiffness, or between changes in stiffness and changes in thickness. In conclusion, the present pilot study showed that ECC altered biomechanical muscle properties, reflected by decreased elastic modulus and dynamic muscle stiffness 24 h after ECC.
Project description:<p>The NHGRI Next Generation Mendelian Genetics project uses exome resequencing to identify variants in unsolved Mendelian diseases.</p> <p>Samples were collected from a single, multi-generational family with the same phenotype of exaggerated muscular development (muscular hypertrophy) and strength characterized by reduced fat pad thickness under the skin. All family members deny "body building" activities, and are so far negative for known gene mutation that have been identified as associated with excessive muscle development. All family members have examples of demonstrating extraordinary strength occurring both in childhood and old age. No negative associated phenotype traits with the muscle hypertrophy phenotype have been identified.</p>
Project description:BackgroundTitin is an elastic sarcomeric filament that has been proposed to play a key role in mechanosensing and trophicity of muscle. However, evidence for this proposal is scarce due to the lack of appropriate experimental models to directly test the role of titin in mechanosensing.MethodsWe used unilateral diaphragm denervation (UDD) in mice, an in vivo model in which the denervated hemidiaphragm is passively stretched by the contralateral, innervated hemidiaphragm and hypertrophy rapidly occurs.ResultsIn wildtype mice, the denervated hemidiaphragm mass increased 48 ± 3% after 6 days of UDD, due to the addition of both sarcomeres in series and in parallel. To test whether titin stiffness modulates the hypertrophy response, RBM20?RRM and Ttn?IAjxn mouse models were used, with decreased and increased titin stiffness, respectively. RBM20?RRM mice (reduced stiffness) showed a 20 ± 6% attenuated hypertrophy response, whereas the Ttn?IAjxn mice (increased stiffness) showed an 18 ± 8% exaggerated response after UDD. Thus, muscle hypertrophy scales with titin stiffness. Protein expression analysis revealed that titin-binding proteins implicated previously in muscle trophicity were induced during UDD, MARP1 & 2, FHL1, and MuRF1.ConclusionsTitin functions as a mechanosensor that regulates muscle trophicity.
Project description:The pathophysiological mechanism of resting tremor in Parkinson's disease remains obscure. Spinal/peripheral mechanisms may modulate oscillatory activity from central origin, thereby changing amplitude and frequency of tremor in Parkinson's disease.