Massage protects skeletal muscle from injury during long-term heavy-duty exercise via integrin ß1 and laminin 2 channels of basement membrane.

BACKGROUND: Massage is widely used in exercise-induced skeletal muscle damage (EIMD). It has been proven that massage can improve the morphology and function of damaged skeletal muscle in multiple ways. However, whether massage can protect skeletal muscles from injury during long-term heavy-duty exercise has not yet been determined. METHODS: In this study, a rat model of overuse injury was established by eccentric running for 4 weeks, and pressing at constant pressure and frequency and massage were used as intervention methods to explore whether massage could protect skeletal muscle from injury through upregulating integrin and the basement membrane laminin. RESULTS: The results showed that compared with the model group, the ultrastructure of skeletal muscle in the massage group was relatively complete and clear, and the maximum isotonic and tetanic contraction forces were significantly increased (P < 0.01). In addition, in the massage group, ß1 integrin expression was significantly increased, p-FAK protein expression was decreased, and the co-localization of ß1 integrin and the basement membrane laminin 2 was significantly increased (P < 0.01). CONCLUSION: Our study shows that during long-term heavy-duty exercise, massage can enhance the cell adhesion function mediated by integrin ß1 and laminin 2 to protect skeletal muscle from injury and prevent the occurrence of overuse injury.

Similar effects of fatigue induced by a repetitive pointing task on local and remote light touch and pain perception in men and women.

BACKGROUND: Women involved in repetitive, fatiguing, jobs develop more neck and/or shoulder musculoskeletal disorders than men. Sex differences in the pain response to exercise could contribute to the higher prevalence of neck/shoulder musculoskeletal disorders in women. The objective of this study was to assess sex differences in pain sensitivity following a fatiguing upper limb task. Relationships between measures of fatigue and of the sensitivity to nociceptive and to non-nociceptive stimulations were also explored. METHODS: Thirty healthy adults (15 women) performed a fatiguing repetitive pointing task with their dominant arm. Upper limb electromyography was recorded from the dominant upper trapezius, anterior deltoid and bicep brachii and from the contralateral tibialis anterior. Before and immediately after the repetitive pointing task, pressure pain and light touch sensitivity thresholds were measured over the same muscles. RESULTS: Electromyographic signs of fatigue were observed only in the anterior deltoid and biceps brachii muscles. Pressure pain thresholds over both muscles increased slightly (effect size ≤ 0.34), but no changes occurred over the upper trapezius and the tibialis anterior. Light touch thresholds increased moderately to importantly after the repetitive pointing task over all four muscles (effect sizes = 0.58 to 0.87). No sex differences were observed in any sensory variable. Moreover, no or weak correlations (r = -0.27 to 0.39) were observed between electromyographical signs of fatigue, light touch threshold and pressure pain threshold variables. CONCLUSIONS: We observed sex-independent effects of a repetitive upper limb task on the sensitivity to painful and to nonpainful stimuli. Moreover, the hypoalgesia induced by the repetitive pointing task was weak and localized, and did not directly correlate with the induced muscle fatigue. Results suggest that fatigue-related changes in the sensitivity to noxious and innocuous stimuli could not explain women's greater prevalence of neck/shoulder musculoskeletal disorders.

Clinical and biochemical characteristics of high-intensity functional training (HIFT) and overtraining syndrome: findings from the EROS study (The EROS-HIFT).

The metabolic and hormonal consequences of high-intensity functional training regimens such as CrossFit® (CF) are unclear. Little is known about the triggers and clinical and biochemical features of CF-related overtraining syndrome (OTS). The EROS study compared endocrine and metabolic responses, and eating, social, psychological and body characteristics of OTS-affected (OTS) and healthy athletes (ATL), and non-physically active controls (NPAC). The current study is a post-hoc analysis of the CF subgroups of the EROS study, to evaluate specific characteristics of CF in ATL and OTS. Parameters were overall and pairwise compared among OTS-affected (CF-OTS) and healthy (CF-ATL) athletes that exclusively practiced CF, and NPAC. CF-ATL yielded earlier and enhanced cortisol, GH, and prolactin responses to an insulin tolerance test (ITT), increased neutrophils, lower lactate, increased testosterone, improved sleep quality, better psychological performance, increased measured-to-predicted basal metabolic rate (BMR) ratio and fat oxidation, and better hydration, when compared to NPAC. Conversely, more than 90% of the adaptive changes in CF were lost under OTS, including an attenuation of the hormonal responses to an ITT, increased estradiol, decreased testosterone, and decreased BMR and fat oxidation; the most remarkable trigger of OTS among "HIFT athletes" was the long-term low carbohydrate and calorie intake.

Overuse injuries in sport: a comprehensive overview.

BACKGROUND: The absence of a single, identifiable traumatic cause has been traditionally used as a definition for a causative factor of overuse injury. Excessive loading, insufficient recovery, and underpreparedness can increase injury risk by exposing athletes to relatively large changes in load. The musculoskeletal system, if subjected to excessive stress, can suffer from various types of overuse injuries which may affect the bone, muscles, tendons, and ligaments. METHODS: We performed a search (up to March 2018) in the PubMed and Scopus electronic databases to identify the available scientific articles about the pathophysiology and the incidence of overuse sport injuries. For the purposes of our review, we used several combinations of the following keywords: overuse, injury, tendon, tendinopathy, stress fracture, stress reaction, and juvenile osteochondritis dissecans. RESULTS: Overuse tendinopathy induces in the tendon pain and swelling with associated decreased tolerance to exercise and various types of tendon degeneration. Poor training technique and a variety of risk factors may predispose athletes to stress reactions that may be interpreted as possible precursors of stress fractures. A frequent cause of pain in adolescents is juvenile osteochondritis dissecans (JOCD), which is characterized by delamination and localized necrosis of the subchondral bone, with or without the involvement of articular cartilage. The purpose of this compressive review is to give an overview of overuse injuries in sport by describing the theoretical foundations of these conditions that may predispose to the development of tendinopathy, stress fractures, stress reactions, and juvenile osteochondritis dissecans and the implication that these pathologies may have in their management. CONCLUSIONS: Further research is required to improve our knowledge on tendon and bone healing, enabling specific treatment strategies to be developed for the management of overuse injuries.

Estrogen and mechanical loading-related regulation of estrogen receptor-ß and apoptosis in tendinopathy.

Female-dominant tendinopathies are musculoskeletal disorders caused by repetitive hand posture and motion; they are considered overuse syndromes. Both external mechanical stress and changes in hormone levels might affect disease progression. We have previously reported that estrogen receptor-ß (ER)-ß expression was associated with the pathogenesis of de Quervain's disease. To study the underlying mechanisms, a cyclic stretching culture system was applied to tendon tissue from ovariectomized (OVX) rats. Furthermore, a collagenase I-induced rat tendinopathy model was established to examine the association of ER-ß with disease progression. Our results showed that ER-ß expression and the number of apoptotic cells were higher and associated with disease severity in rats with tendinopathy. Mechanical stress altered the morphology of primary tenocytes and collagen fiber alignment in tendons, and up-regulated the expression of matrix metalloproteinase-9, ER-ß, and interleukin-1ß, as well as induced apoptosis in tenocytes and tendon tissue from OVX rats. This is the first report on the effects of ER-ß and mechanical stress in tendinopathy. We hope these findings contribute to new pharmacological therapies targeting ER-ß signaling pathways to treat tendon-related diseases.

Excessive training is associated with endoplasmic reticulum stress but not apoptosis in the hypothalamus of mice.

Downhill running-based overtraining model increases the hypothalamic levels of IL-1ß, TNF-α, SOCS3, and pSAPK-JNK. The aim of the present study was to verify the effects of 3 overtraining protocols on the levels of BiP, pIRE-1 (Ser724), pPERK (Thr981), pelF2α (Ser52), ATF-6, GRP-94, caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) proteins in the mouse hypothalamus. The mice were randomized into the control, overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. After the overtraining protocols (i.e., at the end of week 8), hypothalamus was removed and used for immunoblotting. The OTR/down group exhibited increased levels of all of the analyzed endoplasmic reticulum stress markers in the hypothalamus at the end of week 8. The OTR/up and OTR groups exhibited increased levels of BiP, pIRE-1 (Ser724), and pPERK (Thr981) in the hypothalamus at the end of week 8. There were no significant differences in the levels of caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) between the experimental groups at the end of week 8. In conclusion, the 3 overtraining protocols increased the endoplasmic reticulum stress at the end of week 8.

Material heterogeneity in cancellous bone promotes deformation recovery after mechanical failure.

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

Changes in the expression of calcitonin gene-related peptide after exposure to injurious stretch-shortening contractions.

UNLABELLED: One of the factors that can result in musculoskeletal injuries, and time off work, is exposure to repetitive motion. The goal of this study was to determine if skeletal muscle injury induced by exposure to injurious stretch-shortening cycles (iSSCs), resulted in hyperalgesia in the hind limb and changes in calcitonin-gene related peptide (CGRP) immunolabeling in the dorsal root ganglia (DRG) in young and old male rats. METHODS: Young (3months) and old (30months) male Fisher 344×BN F1 rats were anesthetized with isoflurane and the left hind limbs were exposed to 15 sets of 10 SSCs. Control animals were exposed to a single bout of SSCs of equal intensity. Sensitivity to mechanical stimulation was assessed using von Frey filaments prior to beginning the experiment, and on days 2 and 9 following exposure to iSSCs. Rats were euthanized one, 3 or 10days after the exposure. The ipsilateral DRG were dissected from the L4-5 region of the spine, along with the left tibialis anterior (LTA) muscle. RESULTS: Rats exposed to iSSCs were more sensitive to mechanical stimulation than control rats 2days after the exposure, and showed a reduction in peak force 3days after exposure. Changes in sensitivity to pressure were not associated with increases in CGRP labeling in the DRG at 3days. However, 9days after exposure to iSSCs, old rats still displayed an increased sensitivity to mechanical stimulation, and this hyperalgesia was associated with an increase in CGRP immunolabeling in the DRG. Young rats exposed to iSSC did not display a change in CGRP immunolabeling and sensitivity to mechanical stimulation returned to control levels at 10days. CONCLUSIONS: These findings suggest that hyperalgesia seen shortly after exposure to iSSC is not influenced by CGRP levels. However, in cases where recovery from injury may be slower, as it is in older rats, CGRP may contribute to the maintenance of hyperalgesia.

Growth and repair factors, osteoactivin, matrix metalloproteinase and heat shock protein 72, increase with resolution of inflammation in musculotendinous tissues in a rat model of repetitive grasping.

BACKGROUND: Expression of the growth factor osteoactivin (OA) increases during tissue degeneration and regeneration, fracture repair and after denervation-induced disuse atrophy, concomitant with increased matrix metalloproteinases (MMPs). However, OA's expression with repetitive overuse injuries is unknown. The aim of this study was to evaluate: 1) OA expression in an operant rat model of repetitive overuse; 2) expression of MMPs; 3) inflammatory cytokines indicative of injury or inflammation; and 4) the inducible form of heat shock protein 70 (HSPA1A/HSP72) as the latter is known to increase during metabolic stress and to be involved in cellular repair. Young adult female rats performed a high repetition negligible force (HRNF) food retrieval task for up to 6 weeks and were compared to control rats. METHODS: Flexor digitorum muscles and tendons were collected from 22 young adult female rats performing a HRNF reaching task for 3 to 6 weeks, and 12 food restricted control (FRC) rats. OA mRNA levels were assessed by quantitative polymerase chain reaction (qPCR). OA, MMP-1, -2, -3, and -13 and HSP72 protein expression was assayed using Western blotting. Immunohistochemistry and image analysis was used to evaluate OA and HSP72 expression. ELISA was performed for HSP72 and inflammatory cytokines. RESULTS: Flexor digitorum muscles and tendons from 6-week HRNF rats showed increased OA mRNA and protein expression compared to FRC rats. MMP-1, -2 and -3 progressively increased in muscles whereas MMP-1 and -3 increased in tendons with HRNF task performance. HSP72 increased in 6-week HRNF muscles and tendons, compared to controls, and co-localized with OA in the myofiber sarcolemma. IL-1alpha and beta increased transiently in tendons or muscles in HRNF week 3 before resolving in week 6. CONCLUSION: The simultaneous increases of OA with factors involved in tissue repair (MMPs and HSP72) supports a role of OA in tissue regeneration after repetitive overuse.

Effect of overuse-induced tendinopathy on tendon healing in a rat supraspinatus repair model.

Supraspinatus tears often result in the setting of chronic tendinopathy. However, the typical repair model utilizes an acute injury. In recognition of that distinction, our laboratory developed an overuse animal model; however it is unclear whether induced overuse is necessary in the repair model. We studied the repair properties of overuse-induced tendons compared to normal tendons. We hypothesized that histological and mechanical properties would not be altered between the overuse-induced and normal tendons 1 and 4 weeks after repair. Thirty-one adult male Sprague-Dawley rats were subjected to either overuse or cage activity for 4 weeks prior to bilateral supraspinatus tendon repair surgery. Rats were sacrificed at 1 and 4 weeks post-surgery and evaluated for histology and mechanics. Results at 1 week showed no clear histologic changes, but increased inflammatory protein expression in overuse tendons. At 4 weeks, percent relaxation was slightly increased in the overuse group. No other alterations in mechanics or histology were observed. Our results suggest that the effects of the surgical injury overshadow the changes evoked by overuse. Because clinically relevant mechanical parameters were not altered in the overuse group, we conclude that when examining tendons 4 weeks after repair in the classic rat supraspinatus model, inducing overuse prior to surgery is likely to be unnecessary.

Alterations in Whole-Body Insulin Sensitivity Resulting From Repeated Eccentric Exercise of a Single Muscle Group: A Pilot Investigation.

Unaccustomed eccentric exercise using large muscle groups elicits soreness, decrements in physical function and impairs markers of whole-body insulin sensitivity; although these effects are attenuated with a repeated exposure. Eccentric exercise of a small muscle group (elbow flexors) displays similar soreness and damage profiles in response to repeated exposure. However, it is unknown whether damage to small muscle groups impacts upon whole-body insulin sensitivity. This pilot investigation aimed to characterize whole-body insulin sensitivity in response to repeated bouts of eccentric exercise of the elbow flexors. Nine healthy males completed two bouts of eccentric exercise separated by 2 weeks. Insulin resistance (updated homeostasis model of insulin resistance, HOMA2-IR) and muscle damage profiles (soreness and physical function) were assessed before, and 48 h after exercise. Matsuda insulin sensitivity indices (ISI Matsuda) were also determined in 6 participants at the same time points as HOMA2-IR. Soreness was elevated, and physical function impaired, by both bouts of exercise (both p < .05) but to a lesser extent following bout 2 (time x bout interaction, p < .05). Eccentric exercise decreased ISI Matsuda after the first but not the second bout of eccentric exercise (time x bout interaction p < .05). Eccentric exercise performed with an isolated upper limb impairs whole-body insulin sensitivity after the first, but not the second, bout.

[Contemporary approaches in evaluation of pro- and antioxidant status in combined forms of occupational diseases due to functional overstrain].

Complex evaluation covered parameters pro- and antioxidant system in some somatic diseases, mostly in arthrosis and polyneuropathies due to occupational factor of functional overstrain. The results obtained prove influence of prolonged occupational functional overstrain causing excessive free oxidative radicals formation, strain of antioxidant status and subsequent oxidant stress--that is clinically manifested with "mutual burden" syndrome in combined occupational diseases.

Upregulation of BDNF and NGF in cervical intervertebral discs exposed to painful whole-body vibration.

STUDY DESIGN: In vivo study defining expression of the neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in cervical intervertebral discs after painful whole-body vibration (WBV). OBJECTIVE: The goal of this study is to determine if BDNF and NGF are expressed in cervical discs after painful WBV in a rat model. SUMMARY OF BACKGROUND DATA: WBV is a possible source of neck pain and has been implicated as increasing the risk for disc disorders. Typically, aneural regions of painful human lumbar discs exhibit hyperinnervation, suggesting nerve ingrowth as potentially contributing to disc degeneration and pain. BDNF and NGF are upregulated in painfully degenerate lumbar discs and hypothesized to contribute to this pathology. METHODS: Male Holtzman rats underwent 7 days of repeated WBV (15 Hz, 30 min/d) or sham exposures, followed by 7 days of rest. Cervical discs were collected for analysis of BDNF and NGF expression through RT-qPCR and Western blot analysis. Immunohistochemistry also evaluated their regional expression in the disc. RESULTS: Vibration significantly increases BDNF messenger ribonucleic acid (mRNA) levels (P=0.036), as well as total-NGF mRNA (P=0.035). Protein expression of both BDNF (P=0.006) and the 75-kDa NGF (P=0.045) increase by nearly 4- and 10-fold, respectively. Both BDNF mRNA (R=0.396; P=0.012) and protein (R=0.280; P=0.035) levels are significantly correlated with the degree of behavioral sensitivity (i.e., pain) at day 14. Total-NGF mRNA is also significantly correlated with the extent of behavioral sensitivity (R=0.276; P=0.044). Both neurotrophins are most increased in the inner annulus fibrosus and nucleus pulposus. CONCLUSION: The increases in BDNF and NGF in the cervical discs after painful vibration are observed in typically aneural regions of the disc, consistent with reports of its hyperinnervation. Yet, the induction of nerve ingrowth into the disc was not explicitly investigated. Neurotrophin expression also correlates with behavioral sensitivity, suggesting a role for both neurotrophins in the development of disc pain. LEVEL OF EVIDENCE: N/A.

mTORC1 and JNK coordinate phosphorylation of the p70S6K1 autoinhibitory domain in skeletal muscle following functional overloading.

The present project was designed to investigate phosphorylation of p70S6K1 in an animal model of skeletal muscle overload. Within 24 h of male Sprague-Dawley rats undergoing unilateral tenotomy to induce functional overloading of the plantaris muscle, phosphorylation of the Thr³89 and Thr4²¹/Ser4²4 sites on p70S6K1 was significantly elevated. Since the Thr4²¹/Ser4²4 sites are purportedly mammalian target of rapamycin complex 1 (mTORC1) independent, we sought to identify the kinase(s) responsible for their phosphorylation. Initially, we used IGF-I treatment of serum-deprived HEK-293E cells as an in vitro model system, because IGF-I promotes phosphorylation of p70S6K1 on both the Thr³89 and Thr4²¹/Ser4²4 sites in skeletal muscle and in cells in culture. We found that, whereas the mTOR inhibitor TORIN2 prevented the IGF-I-induced phosphorylation of the Thr4²¹/Ser4²4 sites, it surprisingly enhanced phosphorylation of these sites during serum deprivation. JNK inhibition with SP600125 attenuated phosphorylation of the Thr4²¹/Ser4²4 sites, and in combination with TORIN2 both the effect of IGF-I and the enhanced Thr4²¹/Ser4²4 phosphorylation during serum deprivation were ablated. In contrast, both JNK activation with anisomycin and knockdown of the mTORC2 subunit rictor specifically stimulated phosphorylation of the Thr4²¹/Ser4²4 sites, suggesting that mTORC2 represses JNK-mediated phosphorylation of these sites. The role of JNK in mediating p70S6K1 phosphorylation was confirmed in the animal model noted above, where rats treated with SP600125 exhibited attenuated Thr4²¹/Ser4²4 phosphorylation. Overall, the results provide evidence that the mTORC1 and JNK signaling pathways coordinate the site-specific phosphorylation of p70S6K1. They also identify a novel role for mTORC1 and mTORC2 in the inhibition of JNK.

Cyclic strain alters the expression and release of angiogenic factors by human tendon cells.

Angiogenesis is associated with the tissue changes underlying chronic overuse tendinopathy. We hypothesized that repetitive, cyclic loading of human tendon cells would lead to increased expression and activity of angiogenic factors. We subjected isolated human tendon cells to overuse tensile loading using an in vitro model (1 Hz, 10% equibiaxial strain). We found that mechanically stimulated human tendon cells released factors that promoted in vitro proliferation and tube formation by human umbilical vein endothelial cells (HUVEC). In response to cyclic strain, there was a transient increase in the expression of several angiogenic genes including ANGPTL4, FGF-2, COX-2, SPHK1, TGF-alpha, VEGF-A and VEGF-C, with no change in anti-angiogenic genes (BAI1, SERPINF1, THBS1 and 2, TIMP1-3). Cyclic strain also resulted in the extracellular release of ANGPTL4 protein by tendon cells. Our study is the first report demonstrating the induction of ANGPTL4 mRNA and release of ANGPTL4 protein in response to cyclic strain. Tenocytes may contribute to the upregulation of angiogenesis during the development of overuse tendinopathy.

Inhibitors of endopeptidase and angiotensin-converting enzyme lead to an amplification of the morphological changes and an upregulation of the substance P system in a muscle overuse model.

BACKGROUND: We have previously observed, in studies on an experimental overuse model, that the tachykinin system may be involved in the processes of muscle inflammation (myositis) and other muscle tissue alterations. To further evaluate the significance of tachykinins in these processes, we have used inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), substances which are known to terminate the activity of various endogenously produced substances, including tachykinins. METHODS: Injections of inhibitors of NEP and ACE, as well as the tachykinin substance P (SP), were given locally outside the tendon of the triceps surae muscle of rabbits subjected to marked overuse of this muscle. A control group was given NaCl injections. Evaluations were made at 1 week, a timepoint of overuse when only mild inflammation and limited changes in the muscle structure are noted in animals not treated with inhibitors. Both the soleus and gastrocnemius muscles were examined morphologically and with immunohistochemistry and enzyme immunoassay (EIA). RESULTS: A pronounced inflammation (myositis) and changes in the muscle fiber morphology, including muscle fiber necrosis, occurred in the overused muscles of animals given NEP and ACE inhibitors. The morphological changes were clearly more prominent than for animals subjected to overuse and NaCl injections (NaCl group). A marked SP-like expression, as well as a marked expression of the neurokinin-1 receptor (NK-1R) was found in the affected muscle tissue in response to injections of NEP and ACE inhibitors. The concentration of SP in the muscles was also higher than that for the NaCl group. CONCLUSIONS: The observations show that the local injections of NEP and ACE inhibitors led to marked SP-like and NK-1R immunoreactions, increased SP concentrations, and an amplification of the morphological changes in the tissue. The injections of the inhibitors thus led to a more marked myositis process and an upregulation of the SP system. Endogenously produced substances, out of which the tachykinins conform to one substance family, may play a role in mediating effects in the tissue in a muscle that is subjected to pronounced overuse.

Increased mast cell numbers in a calcaneal tendon overuse model.

Tendinopathy is often discovered late because the initial development of tendon pathology is asymptomatic. The aim of this study was to examine the potential role of mast cell involvement in early tendinopathy using a high-intensity uphill running (HIUR) exercise model. Twenty-four male Wistar rats were divided in two groups: running group (n = 12); sedentary control group (n = 12). The running-group was exposed to the HIUR exercise protocol for 7 weeks. The calcaneal tendons of both hind limbs were dissected. The right tendon was used for histologic analysis using Bonar score, immunohistochemistry, and second harmonic generation microscopy (SHGM). The left tendon was used for quantitative polymerase chain reaction (qPCR) analysis. An increased tendon cell density in the runners were observed compared to the controls (P = 0.05). Further, the intensity of immunostaining of protein kinase B, P = 0.03; 2.75 ± 0.54 vs 1.17 ± 0.53, was increased in the runners. The Bonar score (P = 0.05), and the number of mast cells (P = 0.02) were significantly higher in the runners compared to the controls. Furthermore, SHGM showed focal collagen disorganization in the runners, and reduced collagen density (P = 0.03). IL-3 mRNA levels were correlated with mast cell number in sedentary animals. The qPCR analysis showed no significant differences between the groups in the other analyzed targets. The current study demonstrates that 7-week HIUR causes structural changes in the calcaneal tendon, and further that these changes are associated with an increased mast cell density.

Bilateral increase in expression and concentration of tachykinin in a unilateral rabbit muscle overuse model that leads to myositis.

BACKGROUND: Tachykinins can have pro-inflammatory as well as healing effects during tissue reorganization and inflammation. Recent studies report an up-regulation in the expression of the substance P (SP)-preferred receptor, the neurokinin-1 receptor, in marked muscle inflammation (myositis). There is, however, only very little information on the expression patterns and levels of tachykinins in this situation. METHODS: The tachykinin system was analyzed using a rabbit experimental model of muscle overuse, whereby unilateral muscle exercise in combination with electrical stimulation led to muscle derangement and myositis in the triceps surae muscle (experimental length 1-6 weeks). Evaluations were made for both parts of the muscle (soleus and gastrocnemius muscles) in experimental and non-experimental (contralateral) sides. Morphologic evaluation, immunohistochemistry, in situ hybridization and enzyme immunoassay (EIA) analyses were applied. RESULTS: Myositis and muscle derangement occurred focally not only in the experimental side but also in the non-experimental side. In the inflammatory areas (focal myositis areas), there were frequent nerve fibers showing tachykinin-like immunoreactivity and which were parts of nerve fascicles and which were freely dispersed in the tissue. Cells in the inflammatory infiltrates showed tachykinin-like immunoreactivity and tachykinin mRNA expression. Specific immunoreactivity and mRNA expression were noted in blood vessel walls of both sides, especially in focally affected areas. With increasing experimental length, we observed an increase in the degree of immunoreactivity in the vessel walls. The EIA analyses showed that the concentration of tachykinin in the tissue on both sides increased in a time-dependent manner. There was a statistical correlation in the concentration of tachykinin and the level of tachykinin immunoreactivity in the blood vessel walls between experimental and non-experimental sides. CONCLUSIONS: The observations show an up-regulation of the tachykinin system bilaterally during muscle derangement/myositis in response to pronounced unilateral muscle overuse. This up-regulation occurred in inflammatory areas and was related not only to increased tachykinin innervation but also to tachykinin expression in blood vessel walls and inflammatory cells. Importantly, the tachykinin system appears to be an important factor not only ipsilaterally but also contralaterally in these processes.

A multidisciplinary approach to overreaching detection in endurance trained athletes.

In sport, high training load required to reach peak performance pushes human adaptation to their limits. In that process, athletes may experience general fatigue, impaired performance, and may be identified as overreached (OR). When this state lasts for several months, an overtraining syndrome is diagnosed (OT). Until now, no variable per se can detect OR, a requirement to prevent the transition from OR to OT. It encouraged us to further investigate OR using a multivariate approach, including physiological, biomechanical, cognitive, and perceptive monitoring. Twenty-four highly trained triathletes were separated into an overload group and a normo-trained group (NT) during 3 wk of training. Given the decrement of their running performance, 11 triathletes were diagnosed as OR after this period. A discriminant analysis showed that the changes of eight parameters measured during a maximal incremental test could explain 98.2% of the OR state (lactatemia, heart rate, biomechanical parameters and effort perception). Variations in heart rate and lactatemia were the two most discriminating factors. When the multifactorial analysis was restricted to these variables, the classification score reached 89.5%. Catecholamines and creatine kinase concentrations at rest did not change significantly in both groups. Running pattern was preserved and cognitive performance decrement was observed only at exhaustion in OR subjects. This study showed that monitoring various variables is required to prevent the transition between NT and OR. It emphasized that an OR index, which combines heart rate and blood lactate concentration changes after a strenuous training period, could be helpful to routinely detect OR.

Aging contributes to inflammation in upper extremity tendons and declines in forelimb agility in a rat model of upper extremity overuse.

We sought to determine if tendon inflammatory and histopathological responses increase in aged rats compared to young rats performing a voluntary upper extremity repetitive task, and if these changes are associated with motor declines. Ninety-six female Sprague-Dawley rats were used in the rat model of upper extremity overuse: 67 aged and 29 young adult rats. After a training period of 4 weeks, task rats performed a voluntary high repetition low force (HRLF) handle-pulling task for 2 hrs/day, 3 days/wk for up to 12 weeks. Upper extremity motor function was assessed, as were inflammatory and histomorphological changes in flexor digitorum and supraspinatus tendons. The percentage of successful reaches improved in young adult HRLF rats, but not in aged HRLF rats. Forelimb agility decreased transiently in young adult HRLF rats, but persistently in aged HRLF rats. HRLF task performance for 12 weeks lead to increased IL-1beta and IL-6 in flexor digitorum tendons of aged HRLF rats, compared to aged normal control (NC) as well as young adult HRLF rats. In contrast, TNF-alpha increased more in flexor digitorum tendons of young adult 12-week HRLF rats than in aged HRLF rats. Vascularity and collagen fibril organization were not affected by task performance in flexor digitorum tendons of either age group, although cellularity increased in both. By week 12 of HRLF task performance, vascularity and cellularity increased in the supraspinatus tendons of only aged rats. The increased cellularity was due to increased macrophages and connective tissue growth factor (CTGF)-immunoreactive fibroblasts in the peritendon. In conclusion, aged rat tendons were overall more affected by the HRLF task than young adult tendons, particularly supraspinatus tendons. Greater inflammatory changes in aged HRLF rat tendons were observed, increases associated temporally with decreased forelimb agility and lack of improvement in task success.