Does glucocorticoid exposure explain the association between metabolic dysfunction and tendinopathy?

BACKGROUND: While metabolic health is acknowledged to affect connective tissue structure and function, the mechanisms are unclear. Glucocorticoids are present in almost every cell type throughout the body and control key physiological processes such as energy homeostasis, stress response, inflammatory and immune processes, and cardiovascular function. Glucocorticoid excess manifests as visceral adiposity, dyslipidaemia, insulin resistance, and type 2 diabetes. As these metabolic states are also associated with tendinopathy and tendon rupture, it may be that glucocorticoids excess is the link between metabolic health and tendinopathy. OBJECTIVE: To synthesise current knowledge linking glucocorticoids exposure to tendon structure and function. METHODS: Narrative literature review. RESULTS: We provide an overview of endogenous glucocorticoid production, regulation, and signalling. Next we review the impact that oral glucocorticoid has on risk of tendon rupture and the effect that injected glucocorticoid has on resolution of symptoms. Then we highlight the clinical and mechanistic overlap between tendinopathy and glucocorticoid excess in the areas of visceral adiposity, dyslipidaemia, insulin resistance and type 2 diabetes. In these areas, we highlight the role of glucocorticoids and how these hormones might underpin the connection between metabolic health and tendon dysfunction. CONCLUSIONS: There are several plausible pathways through which glucocorticoids might mediate the connection between metabolic health and tendinopathy.

Quality-of-Life in Achilles Tendinopathy: An Exploratory Study.

OBJECTIVE: This research aimed to explore the quality-of-life and experiences of people with Achilles tendinopathy. DESIGN: This mixed-methods research used the 8-dimension Assessment of Quality-of-Life (AQoL-8D), focus groups and grounded theory analysis. AQoL-8D scores were compared with population normative scores. In focus groups, participants discussed their experiences with Achilles tendinopathy. SETTING: An online survey was completed, followed by focus groups and interviews held at the University of Canberra. PARTICIPANTS: Adults with Achilles tendon pain were eligible to participate in the online survey, which was distributed through email and social media. RESULTS: Complete survey responses were obtained from 92 individuals, and 11 individuals participated in focus groups and interviews. AQoL-8D scores were significantly lower in those with Achilles tendinopathy (79 ± 11 vs 81 ± 13). AQoL-8Ds of mental health, pain, senses, and the physical "super dimension" were also significantly lower. The difference exceeded the AQoL-8D minimum clinically important difference of 6% only for the pain dimension. Themes identified included adapting lifestyles, living with the condition, changes in mental and social well-being, conflict with identity, frustration, and individual experiences. CONCLUSIONS: Achilles tendinopathy is associated with a lower quality-of-life score, but on average, the difference does not exceed the minimum clinically important difference. In focus groups, some individuals described profound impacts on their life. This discrepancy likely reflects the variability of the impact across individuals. For some people, the effect is minimal, yet for those who tie their identity and social activities to fitness and physical activity, the effect can be profound.

Vertebral Artery Dissection in Sport: A Systematic Review.

BACKGROUND: Vertebral artery dissection (VAD) is a potentially catastrophic injury that may occur during sports participation. A comprehensive review is needed to collate documented cases to improve understanding and inform future preventative approaches. OBJECTIVE: This review aimed to understand the extent of VAD in sport and characterise trends suggestive of mechanisms of injury. METHODS: Electronic databases were searched using terms related to VAD and sport. Records were included if they described one or more cases of VAD attributed to sport. RESULTS: A total of 79 records described 128 individual cases of VAD in sport, of which 118 were confirmed by imaging or autopsy and included in analyses. Cases were attributed to 43 contact and non-contact sports. The median age of cases was 33 years (IQR 22-44), and 75% were male. There were 22 cases of fatal injury, of which ten involved an impact to the mastoid region and seven involved an impact to the head or neck. Non-fatal cases of VAD were attributed to impact to the head or neck (not mastoid region), movement or held position without impact, and in some cases no reported incident. CONCLUSIONS: VAD attributed to sports participation is uncommonly reported and the mechanisms are varied. Impact to the mastoid region is consistently implicated in fatal cases and should be the focus of injury prevention strategies in sport. Efforts may also be directed at improving the prognosis of cases with delayed presentation through clinical recognition and imaging. The review was registered on the international prospective register for systematic reviews ( http://www.crd.york.ac.uk/PROSPERO ) (CRD42018090543).

Clinical Improvements Are Not Explained by Changes in Tendon Structure on Ultrasound Tissue Characterization After an Exercise Program for Patellar Tendinopathy.

OBJECTIVES: The aim of this study was to investigate the effects of a 4-wk in-season exercise program of isometric or isotonic exercises on tendon structure and dimensions as quantified by ultrasound tissue characterization (UTC). DESIGN: This was a randomized clinical trial. Volleyball and basketball players (16-31 yrs, n = 29) with clinically diagnosed patellar tendinopathy were randomized to a 4-wk isometric or isotonic exercise program. The programs were designed to decrease patellar tendon pain. A baseline and 4-wk UTC scan was used to evaluate change in tendon structure. RESULTS: No significant change in tendon structure or dimensions on UTC was detected after the exercise program despite patellar tendinopathy symptoms improving. The percentage and mean cross-sectional area of aligned fibrillar structure (echo types I + II) (Z = -0.414, P = 0.679) as well as disorganized structure (echo types III + IV) (Z = -0.370, P = 0.711) did not change over the 4-wk exercise program. Change in tendon structure and dimensions on UTC did not differ significantly between the groups. CONCLUSION: Structural properties and dimensions of the patellar tendon on UTC did not change after a 4-wk isometric or isotonic exercise program for athletes with patellar tendinopathy in-season, despite an improvement in symptoms. It seems that structural improvements are not required for a positive clinical outcome.

Physiotherapists use a small number of behaviour change techniques when promoting physical activity: A systematic review comparing experimental and observational studies.

OBJECTIVES: Physiotherapists promote physical activity as part of their practice. This study reviewed the behaviour change techniques physiotherapists use when promoting physical activity in experimental and observational studies. DESIGN: Systematic review of experimental and observational studies. METHODS: Twelve databases were searched using terms related to physiotherapy and physical activity. We included experimental studies evaluating the efficacy of physiotherapist-led physical activity interventions delivered to adults in clinic-based private practice and outpatient settings to individuals with, or at risk of, non-communicable diseases. Observational studies reporting the techniques physiotherapists use when promoting physical activity were also included. The behaviour change techniques used in all studies were identified using the Behaviour Change Technique Taxonomy. The behaviour change techniques appearing in efficacious and inefficacious experimental interventions were compared using a narrative approach. RESULTS: Twelve studies (nine experimental and three observational) were retained from the initial search yield of 4141. Risk of bias ranged from low to high. Physiotherapists used seven behaviour change techniques in the observational studies, compared to 30 behaviour change techniques in the experimental studies. Social support (unspecified) was the most frequently identified behaviour change technique across both settings. Efficacious experimental interventions used more behaviour change techniques (n=29) and functioned in more ways (n=6) than did inefficacious experimental interventions (behaviour change techniques=10 and functions=1). CONCLUSIONS: Physiotherapists use a small number of behaviour change techniques. Less behaviour change techniques were identified in observational studies compared to experimental studies, suggesting physiotherapists use less BCTs clinically than experimentally.

Physiotherapist-Led Physical Activity Interventions Are Efficacious at Increasing Physical Activity Levels: A Systematic Review and Meta-analysis.

OBJECTIVE: Physical activity (PA) interventions to address noncommunicable disease (NCD) risk are commonly delivered in private practice and outpatient physiotherapy settings. This study reviewed the efficacy of physiotherapist-led physical activity (PLPA) interventions at improving PA levels. DATA SOURCES: Twelve databases were searched using terms related to both physiotherapy and PA. English-language studies of all designs in adults were included. Meta-analyses were conducted separately for interventions measuring the following: (1) participants meeting recommended PA levels; (2) total PA at short- and long-term follow-up; and (3) total PA achieved after short and long PLPA interventions. Pooled effects were calculated using a fixed-effects model as standardized mean differences (SMDs). Nonstatistical analysis was used to identify the effect of PLPA interventions on the volume of PA performed at different intensities. MAIN RESULTS: From an initial 4140 studies, 8 were retained, and risk of bias ranged from low to high. Meta-analysis showed the odds of adults meeting minimum recommended PA levels were doubled in groups provided a PLPA intervention [OR = 2.15, 95% confidence interval (CI) = 1.35-3.43]. Total PA levels were increased in the short term (SMD = 0.15, 95% CI = 0.03-0.27) but not in the long term. Longer term interventions did not improve outcomes. Nonstatistical analysis identified that PLPA interventions were efficacious at increasing the amount of PA adults performed at all intensities. CONCLUSIONS: Clinic-based PLPA interventions delivered in private practice, primary care, and outpatient settings were efficacious at increasing PA in adults at risk of NCDs. Improvements did not last long term and were not enhanced with longer interventions.

Effects of Altering Trunk Position during Landings on Patellar Tendon Force and Pain.

PURPOSE: This study aimed to verify the immediate effects of altering sagittal plane trunk position during jump landings on lower limb biomechanics, patellar tendon force, and pain of athletes with and without patellar tendinopathy. METHODS: Twenty-one elite male athletes were categorized into three groups: athletes with patellar tendinopathy (TG; n = 7), asymptomatic athletes with patellar tendon abnormalities (n = 7), and asymptomatic athletes without tendon abnormalities (CG; n = 7). A biomechanical evaluation was conducted while the athletes performed drop landings from a bench in a self-selected trunk position (SS). Afterward, the athletes were randomly assigned to land with either a flexed trunk position (FLX) or an extended trunk position (EXT). Variables of interest for this study included sagittal plane peak kinematics, kinetics, patellar tendon force, and pain during the landing tasks. RESULTS: Peak patellar tendon force, knee extensor moment, and knee pain decreased in the FLX landing compared with the SS landing, regardless of group. In addition, peak patellar tendon force, knee extensor moment, and vertical ground reaction force were smaller in the FLX landing compared with the EXT landing. The TG had smaller peak ankle dorsiflexion compared with the CG during jump landings, regardless of trunk position. CONCLUSIONS: Landing with greater trunk flexion decreased patellar tendon force in elite jumping athletes. An immediate decrease in knee pain was also observed in symptomatic athletes with a more flexed trunk position during landing. Increasing trunk flexion during landing might be an important strategy to reduce tendon overload in jumping athletes.

Continuing Professional Development via Social Media or Conference Attendance: A Cost Analysis.

BACKGROUND: Professional development is essential in the health disciplines. Knowing the cost and value of educational approaches informs decisions and choices about learning and teaching practices. OBJECTIVE: The primary aim of this study was to conduct a cost analysis of participation in continuing professional development via social media compared with live conference attendance. METHODS: Clinicians interested in musculoskeletal care were invited to participate in the study activities. Quantitative data were obtained from an anonymous electronic questionnaire. RESULTS: Of the 272 individuals invited to contribute data to this study, 150 clinicians predominantly from Australia, United States, United Kingdom, India, and Malaysia completed the outcome measures. Half of the respondents (78/150, 52.0%) believed that they would learn more with the live conference format. The median perceived participation costs for the live conference format was Aus $1596 (interquartile range, IQR 172.50-2852.00). The perceived cost of participation for equivalent content delivered via social media was Aus $15 (IQR 0.00-58.50). The majority of the clinicians (114/146, 78.1%, missing data n=4) indicated that they would pay for a subscription-based service, delivered by social media, to the median value of Aus $59.50. CONCLUSIONS: Social media platforms are evolving into an acceptable and financially sustainable medium for the continued professional development of health professionals. When factoring in the reduced costs of participation and the reduced loss of employable hours from the perspective of the health service, professional development via social media has unique strengths that challenge the traditional live conference delivery format.

The relationship of hip muscle performance to leg, ankle and foot injuries: a systematic review.

OBJECTIVES: Hip control affects movement and muscle firing patterns in the leg, ankle and foot, and may contribute to overuse injuries. Muscle performance can be measured as strength, endurance or muscle activation patterns. Our objective was to systematically review whether hip muscle performance is associated with leg, ankle and foot injuries. DATA SOURCES: A structured and comprehensive search of six medical literature databases was combined with forward and backward citation tracking (AMED, CINAHL, EMBASE, Medline, Scopus and SportDiscus). STUDY SELECTION: Eligible studies measured hip muscle performance in individuals with musculoskeletal injuries below the tibial tuberosity, using dynamometry or electromyography (EMG). All studies compared an injured group with a control group or compared the injured and non-injured limb in the same individual. DATA EXTRACTION: Data was extracted from each study independently by two authors. DATA SYNTHESIS: Twenty case-control and four prospective studies (n = 24) met the inclusion criteria. Injury classifications included chronic ankle instability (n = 18), Achilles tendinopathy (n = 2), medial tibial stress syndrome and tibial stress fracture (n = 1), posterior tibial tendon dysfunction (n = 1), and exertional medial tibial pain (n = 2). Eleven of the studies revealed differences in hip muscle performance indicating less strength, delayed onset activation and decreased duration of activation in the injured groups. Two studies found evidence for differences between groups only in some of their measurements. Three out of the four prospective studies revealed that hip muscle performance was not a risk factor for leg, ankle and foot injuries. CONCLUSIONS: This review provides limited evidence that hip muscle performance variables are related to leg, ankle and foot injuries. Emerging evidence indicates this might be a result of the injury rather than a contributor to the injury.

Translating evidence to practice in the health professions: a randomized trial of Twitter vs Facebook.

Objective: Our objective was to compare the change in research informed knowledge of health professionals and their intended practice following exposure to research information delivered by either Twitter or Facebook. Methods: This open label comparative design study randomized health professional clinicians to receive "practice points" on tendinopathy management via Twitter or Facebook. Evaluated outcomes included knowledge change and self-reported changes to clinical practice. Results: Four hundred and ninety-four participants were randomized to 1 of 2 groups and 317 responders analyzed. Both groups demonstrated improvements in knowledge and reported changes to clinical practice. There was no statistical difference between groups for the outcomes of knowledge change (P = .728), changes to clinical practice (P = .11) or the increased use of research information (P = .89). Practice points were shared more by the Twitter group (P < .001); attrition was lower in the Facebook group (P < .001). Conclusion: Research information delivered by either Twitter or Facebook can improve clinician knowledge and promote behavior change. No differences in these outcomes were observed between the Twitter and Facebook groups. Brief social media posts are as effective as longer posts for improving knowledge and promoting behavior change. Twitter may be more useful in publicizing information and Facebook for encouraging course completion.

What tendon pathology is seen on imaging in people who have taken fluoroquinolones? A systematic review.

Fluoroquinolones (FQs) are highly effective broad-spectrum antibiotics. Clinical data reveal an increased incidence of tendon pain and rupture in those taking FQs, yet little is known about tendon structural changes. This review synthesises published data on tendon structural changes in people who have taken FQs. Eight databases were searched for potentially relevant articles (Medline, CINAHL, Biological Abstracts, AMED, Web of Knowledge, SCOPUS, SportDiscus and EMBASE) using MeSH and free-text searches. Inclusion and exclusion criteria determined which articles were used for this review. Twenty-six papers met the eligibility criteria. The Achilles tendon was most commonly affected, and ciprofloxacin and levofloxacin were the most commonly implicated FQs. Mean time to onset of symptoms was 16 days following first FQ dose. Imaging modalities used included magnetic resonance imaging (MRI), B-mode ultrasound (US) and computed tomography (CT). Tendon measurements were rarely reported, and intratendinous imaging findings were not reported in a consistent manner. Few studies imaged tendons bilaterally, and only two studies were longitudinal in design. Future studies should report imaging measures such as thickness and cross-sectional area and use consistent descriptions of intratendinous changes during and post-FQ treatment.

Infant and toddler drowning in Australia: Patterns, risk factors and prevention recommendations.

Drowning is a leading cause of death among infants and toddlers. Unique physiological and behavioural factors contribute to high mortality rates. Drowning incidents predominantly occur during warmer months and holidays. Recent studies link high socio-economic status and drowning, in contrast to earlier studies. Cardiac arrhythmias, epilepsy and autism are strong risk factors for drowning incidents. Prevention strategies have substantially lowered drowning rates. While legislation-compliant pool fencing substantially reduces drowning risk, compliance levels are low, and penalties are minor. Active supervision education for parents and carers is an effective drowning prevention strategy. Bystanders provide basic life support in only 30% of cases; strategies to increase training uptake are needed. Fencing costs should be a mandatory inclusion for pool installations, with high penalties for non-compliance. Basic life support training should be compulsory for pool owners, and tax incentives should be used as a lever to increase training uptake.

A pilot study on biomarkers for tendinopathy: lower levels of serum TNF-α and other cytokines in females but not males with Achilles tendinopathy.

BACKGROUND: Achilles tendinopathy is a painful musculoskeletal condition that is common among athletes, and which limits training capacity and competitive performance. The lack of biomarkers for tendinopathy limits research into risk factors and also the evaluation of new treatments. Cytokines and growth factors involved in regulating the response of tendon cells to mechanical load have potential as biomarkers for tendinopathy. METHODS: This case-control study compared serum concentration of cytokines and growth factors (TNF-α, IL-1ß, bFGF, PDFG-BB, IFN-γ, VEGF) between individuals with chronic Achilles tendinopathy and controls. These were measured in fasting serum from 22 individuals with chronic Achilles tendinopathy and 10 healthy controls. Results were analysed in relation to gender and physical activity pattern. RESULTS: TNF-α concentration was lower in the entire tendinopathy group compared with the entire control group; none of the other cytokines were significantly different. TNF-α levels were nevertheless highly correlated with the other cytokines measured, in most of the subgroups. Analysed by gender, TNF-α and PDGF-BB concentrations were lower in the female tendinopathy group but not the male tendinopathy group. A trend was seen for lower IL-1ß in the female tendinopathy group. Physical activity was correlated with TNF-α, PDGF-BB and IL-1ß to varying extents for control subgroups, but not for the female tendinopathy group. No correlations were seen with BMI or duration of symptoms. CONCLUSIONS: This pilot study indicates a lower level of TNF-α and PDGF-BB, and to some extent IL-1ß among females, but not males, in the chronic phase of Achilles tendinopathy. It is suggested that future studies on tendinopathy biomarkers analyse male and female data separately. The lack of correlation between cytokine level and physical activity in the female tendinopathy group warrants further study.

Do isometric and isotonic exercise programs reduce pain in athletes with patellar tendinopathy in-season? A randomised clinical trial.

OBJECTIVES: Many athletes with patellar tendinopathy participate in sports with symptoms during or after activities. Current treatments do not decrease pain in-season; eccentric exercises in-season result in an increase in pain. This study examined if isometric and isotonic exercises relieved pain in competing athletes with patellar tendinopathy. DESIGN: Randomised clinical trial. METHODS: Jumping athletes with patellar tendinopathy playing at least three times per week participated in this study. Athletes were randomised into an isometric or isotonic exercise group. The exercise programs consisted of four isometric or isotonic exercise sessions per week for four weeks. Pain during a single leg decline squat (SLDS) on a Numeric Rating Scale (NRS; 0-10) was used as the main outcome measure; measurements were completed at baseline and at 4-week follow-up. RESULTS: Twenty-nine athletes were included in this study. Median pain scores improved significantly over the 4-week intervention period in both the isometric group (Z=-2.527, p=0.012, r=-0.63) and isotonic group (Z=-2.952, p=0.003, r=-0.63). There was no significant difference in NRS pain score change (U=29.0, p=0.208, r=0.29) between the isometric group (median (IQR), 2.5 (1-4.5)) and isotonic group (median (IQR), 3.0 (2-6)). CONCLUSIONS: This is the first study to show a decrease in patellar tendon pain without a modification of training and competition load and the first study to investigate isometric exercises in a clinical setting. Both isometric and isotonic exercise programs are easy-to-use exercises that can reduce pain from patellar tendinopathy for athletes in-season.

Does type 1 diabetes mellitus affect Achilles tendon response to a 10 km run? A case control study.

BACKGROUND: Achilles tendon structure deteriorates 2-days after maximal loading in elite athletes. The load-response behaviour of tendons may be altered in type 1 diabetes mellitus (T1DM) as hyperglycaemia accelerates collagen cross-linking. This study compared Achilles tendon load-response in participants with T1DM and controls. METHODS: Achilles tendon structure was quantified at day-0, day-2 and day-4 after a 10 km run. Ultrasound tissue characterisation (UTC) measures tendon structural integrity by classifying pixels as echo-type I, II, III or IV. Echo-type I has the most aligned collagen fibrils and IV has the least. RESULTS: Participants were 7 individuals with T1DM and 10 controls. All regularly ran distances greater than 5 km and VISA-A scores indicated good tendon function (T1DM = 94 ± 11, control = 94 ± 10). There were no diabetic complications and HbA1c was 8.7 ± 2.6 mmol/mol for T1DM and 5.3 ± 0.4 mmol/mol for control groups. Baseline tendon structure was similar in T1DM and control groups - UTC echo-types (I-IV) and anterior-posterior thickness were all p > 0.05. No response to load was seen in either T1DM or control group over the 4-days post exercise. CONCLUSION: Active individuals with T1DM do not have a heightened Achilles tendon response to load, which suggests no increased risk of tendon injury. We cannot extrapolate these findings to sedentary individuals with T1DM.

Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review.

BACKGROUND: Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. OBJECTIVE: To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. METHODS: We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases-MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case-control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. RESULTS: 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and -0.19 mmol/L, respectively. CONCLUSIONS: The results of this review indicate that a relationship exists between an individual's lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy.

The acceptability among health researchers and clinicians of social media to translate research evidence to clinical practice: mixed-methods survey and interview study.

BACKGROUND: Establishing and promoting connections between health researchers and health professional clinicians may help translate research evidence to clinical practice. Social media may have the capacity to enhance these connections. OBJECTIVE: The aim of this study was to explore health researchers' and clinicians' current use of social media and their beliefs and attitudes towards the use of social media for communicating research evidence. METHODS: This study used a mixed-methods approach to obtain qualitative and quantitative data. Participation was open to health researchers and clinicians. Data regarding demographic details, current use of social media, and beliefs and attitudes towards the use of social media for professional purposes were obtained through an anonymous Web-based survey. The survey was distributed via email to research centers, educational and clinical institutions, and health professional associations in Australia, India, and Malaysia. Consenting participants were stratified by country and role and selected at random for semistructured telephone interviews to explore themes arising from the survey. RESULTS: A total of 856 participants completed the questionnaire with 125 participants declining to participate, resulting in a response rate of 87.3%. 69 interviews were conducted with participants from Australia, India, and Malaysia. Social media was used for recreation by 89.2% (749/840) of participants and for professional purposes by 80.0% (682/852) of participants. Significant associations were found between frequency of professional social media use and age, gender, country of residence, and graduate status. Over a quarter (26.9%, 229/852) of participants used social media for obtaining research evidence, and 15.0% (128/852) of participants used social media for disseminating research evidence. Most participants (95.9%, 810/845) felt there was a role for social media in disseminating or obtaining research evidence. Over half of the participants (449/842, 53.3%) felt they had a need for training in the use of social media for professional development. A key barrier to the professional use of social media was concerns regarding trustworthiness of information. CONCLUSIONS: A large majority of health researchers and clinicians use social media in recreational and professional contexts. Social media is less frequently used for communication of research evidence. Training in the use of social media for professional development and methods to improve the trustworthiness of information obtained via social media may enhance the utility of social media for communicating research evidence. Future studies should investigate the efficacy of social media in translating research evidence to clinical practice.

The sympathetic nervous system and tendinopathy: a systematic review.

BACKGROUND: Tendinopathy is a clinical diagnosis of localised tendon pain often confirmed by imaging findings. The pathophysiological cause of the pain is unknown and the sympathetic nervous system (SNS) may be implicated. OBJECTIVE: To review what is known regarding the role of the SNS in human tendinopathy. STUDY SELECTION: Published data describing sympathetic innervation or an index of sympathetic activity in human tendons were eligible for inclusion. DATA SOURCES: Bibliographical databases (AMED, Biological Abstracts, CINAHL Plus, EMBASE, MEDLINE, Scopus, SPORTDiscus and Web of Science) were searched for relevant articles. Reference lists from included articles were screened for additional articles. STUDY APPRAISAL: Studies were scored with a quality assessment tool to identify potential sources of bias. Each question had an explicit decision rule to guide assessment. RESULTS: Nine case-control and four cross-sectional studies examined sympathetic innervation of tendons. There was evidence suggesting a lack of difference in sympathetic innervation of tendon proper between tendinopathy biopsies and healthy controls. In contrast, the paratendinous tissue showed evidence of increased sympathetic innervation in painful tendons. The most notable increase in SNS markers was seen in abnormal tenocytes from painful tendons. Data from two studies were suitable for meta-analysis. These heterogeneous studies revealed no difference in sympathetic innervation between painful and pain-free tendons. No studies recorded SNS activity in vivo. CONCLUSION: Sympathetic innervation in painful tendons depends on tissue type. Abnormal tenocytes may have increased capacity for self-production of sympathetic neurotransmitters. Future insight may be gained by measuring global in vivo sympathetic drive in tendinopathy.

Evidence of the TNF-α system in the human Achilles tendon: expression of TNF-α and TNF receptor at both protein and mRNA levels in the tenocytes.

UNLABELLED: Understanding adaption to load is essential for prevention and treatment of tendinopathy/tendinosis. Cytokine release in response to load is one mechanism involved in mechanotransduction. The cytokine tumor necrosis factor alpha (TNF-α) is implicated in tendinosis and can induce apoptotic effects via tumor necrosis factor receptor 1 (TNFR1). The complete absence of information concerning the TNF-α system in Achilles tendon is a limitation as mid-portion Achilles tendinosis is very frequent. PURPOSE: To examine expression patterns of TNF-α and its two receptors (TNFR1 and TNFR2) in human Achilles tendinosis and control tissue and to biochemically confirm the presence of TNF-α in tendinosis tissue. METHODS: TNF-α and TNFR1 mRNA were detected via in situ hybridization. TNF-α, TNFR1, and TNFR2 were demonstrated immunohistochemically. Apoptosis markers were utilized. ELISA was used to detect TNF-α. RESULTS: TNF-α and TNFR1 mRNA was detected in tenocytes of both tendinosis and control tendons. Tenocytes from both groups displayed specific immunoreactions for TNF-α, TNFR1, and TNFR2. The widened/rounded tenocytes of tendinosis samples exhibited the most intense immunoreactions. Apoptosis was detected in only a subpopulation of the tenocytes in tendinosis tissue. TNF-α was measurable in tendinosis tissue. Inflammatory cells were not seen. CONCLUSION: This is the first evidence of the existence of the TNF-α system in the human Achilles tendon. Findings are confirmed at mRNA and protein levels as well as biochemically. The TNF-α system was in principle confined to the tenocytes. The connection between tenocyte morphology and the expression pattern of TNF-α, TNFR1, and TNFR2 suggests that the TNF-α system may be involved in tenocyte activation in Achilles tendinosis.