The aetiology of pain in chronic midportion Achilles tendinopathy

Background Achilles tendinopathy (AT) is a common injury in athletes and sedentary individuals, which presents as pain and loss of function in the lower limb. Tendon pathology can exist without pain, but the hallmark of the condition is pain, which is classically of insidious onset, related to loading activity and often resistant to treatment. While the biology of pain in general is well described, the mechanisms of pain in AT are not fully understood. Most commonly, the nociceptive driver associated with AT is thought to be a result of the structural changes that occur in the tendon or the inflammatory cascades that occur in the pathological tendon and/or reflective of altered central pain mechanisms. Evidence from other chronic pain conditions also shows that genetic variation explains, at least in part, some of the heterogeneity observed in chronic pain conditions. The presentation of chronic Achilles tendon pain is variable and therefore it is reasonable to propose that this variability may be influenced by a genetic component. The absence of a definitive cause or mechanism of pain in AT is reflected in the plethora of treatment strategies available to manage it, most of which are not universally effective. In order to improve the management of pain in chronic AT, it is imperative that its mechanisms be better understood. Aims of the thesis The aims of this thesis were therefore to characterise Achilles tendon pain using other pain questionnaires, to investigate the relationship between structural changes and central pain mechanisms with self-reported tendon pain. Additionally, the thesis sought to evaluate the relationship between selected gene variants and pain in a cohort of recreational athletes with chronic Achilles tendinopathy using a candidate gene approach. Candidate genes: COMT rs4818 (C/G), COMT rs4633 (C/T), TAC1rs2072100 (C/T), TACR1 rs3771829 (C/G) and SCN9A rs6746030 (G/A) were selected based on the biological function of their encoded proteins within the pain pathways. The objectives of the specific chapters which addressed these aims were: • Describe Achilles tendon pain using multidimensional pain scales; the short forms of the McGill pain questionnaire (sf-MPQ) and Brief Pain Inventory (sf-BPI), as well as the Victorian Institute of Sports Assessment – Achilles questionnaire (VISA-A) (Chapter 2). • Evaluate the relationship between self- reported tendon pain, the grey scale ultrasound and colour Doppler characteristics in chronic AT (Chapter 3). • Evaluate the relationship between conditioned pain modulation and chronic AT (Chapter 4). • Explore and evaluate if variants in genes [COMT rs4818 (C/G), COMT rs4633 (C/T), TAC1 rs2072100 (C/T), TACR1 rs3771829 (C/G) and SCN9A rs6746030 (G/A)] involved in the pain pathways are associated with either self-reported tendon pain and/or conditioned pain modulation (Chapter 5). Methods Two hundred and eighty-two (282) recreational athletes with at least one year's experience in their main sport were recruited for the studies in this thesis but fifty-two (52) were excluded for not meeting the inclusion criteria of the studies. Hence, 103 recreational athletes without a history of chronic AT (CON) and 127 participants clinically diagnosed with chronic AT (TEN) were included in the study. All participants completed demographic questionnaires on their medical, sporting, training, and injury history. Participants with AT (TEN) also completed the self-administered eight question VISA-A questionnaire, the sf-MPQ and the sf-BPI. Additionally, all participants had grey scale ultrasound (US) and colour Doppler (CD) assessments of both their tendons performed and had conditioned pain modulation (CPM) assessed using pressure and cold pain. Lastly, participants were genotyped for variants in COMT rs4818 (C/G), COMT rs4633 (C/T), TAC1 rs2072100 (C/T), TACR1 rs3771829 (C/G) and SCN9A rs6746030 (G/A) using standard PCR methods. Data were analysed using Statistica Version 13.2.50. Normality of data was assessed using the Shapiro-Wilks test. Evaluations of differences between normally distributed quantitative data were conducted with the independent students t-test or one-way ANOVA, while Mann-Whitney-U and Kruskall-Wallis tests were used for non-normally distributed data. The Fisher's exact and χ2 tests were used for categorical data. For post-hoc analyses, the Kruskal-Wallis associated multiple comparisons test with Bonferroni adjustment was used for quantitative data. For the genotyping data, Hardy– Weinberg equilibrium (HWE) was calculated using ‘HardyWeinberg' version 1.6.3. package. The overall level of significance was set at p0.3; p0.05). However, the median interference index scores of the VISA-A questionnaire of participants with US abnormalities [median (IQR)] [35.5 (30.0 - 41.0), n=36] was significantly higher than those without US abnormalities [32.5 (26.0 - 37.0), n=39, p=0.046]. Additionally, participants from the TEN group who reported no stabbing pain, those who reported mild, moderate or severe stabbing pain on the sf-MPQ had significantly thicker tendons [median (IQR)] [6.0mm (5.2 - 7.6) vs 7.0mm (5.9 - 8.9), 7.7mm (6.2 - 9.1) and 6.3mm (4.9 - 7.4), p=0.037]. From the CPM analysis, participants with tendinopathy had a lower pressure pain threshold (PPT) before [median (IQR)] [TEN: 417kPa (364 - 516) vs CON 601kPa (459 - 724), p<0.001] and during [TEN: 458kPa (358 - 550) vs CON 633kPa (506 - 753), p<0.001] the cold pressor test. However, there was no difference in the CPM effect between the two groups [median (IQR)] [TEN: 34kPa (-2 - 79) vs CON: 45kPa (4 - 94), p=0.490]. From the sf-BPI, PPT before the cold pressor test were significantly lower in individuals who reported mild to severe interferences in mood (p=0.023), general activity (p=0.038) and walking ability (p=0.004) when compared to those who reported no interferences. Pressure pain thresholds before the cold pressor test were also significantly lower in those participants who reported mild to severe pain at the time of testing (p=0.024) or reported moderate to severe pain on average (p=0.014) on the sf- BPI. Additionally, from the sf-BPI, a low CPM effect was significantly associated with mild to severe interference with sleep (p=0.043). The genotype analysis showed that the median total scores of self-reported tendon pain from the sf-MPQ were significantly different (p=0.019) among the three COMT rs4818 (G/C) genotype groups [median (IQR)] [CC: 9.1 (4.0 - 13.0) n=61; CG: 7.3 (4.0 - 0.0) n=50; GG: 4.0 (1.0 - 5.0) n=7], with the CC genotype having a significantly higher pain score (p=0.018) than the GG genotype. No other associations were observed between genotype distributions of COMT rs4633, TAC1 rs2072100, TACR1 rs3771829, SCN9A rs746030 and the median self-reported total tendon pain scores for the sf-MPQ, sf-BPI, VISA-A, or their subscales. Conclusion The novel findings of this thesis suggest that the language of chronic AT pain ought to be further investigated as it may help extend our knowledge of the underlying mechanisms in chronic AT pain. In addition, that AT pain interferes with more than physical and sporting ability should be considered in the overall management of this condition in athletes. While no associations were observed between imaging findings and tendon pain, the relationship between imaging findings and physical limitations suggests that using pain as a primary outcome measure in rehabilitation may be insufficient and highlights the need to further study the relationship between tendon structure, imaging and pain. Furthermore, impaired CPM was associated with interferences with sleep which suggests that, though not quite clear, some central mechanisms are at play in chronic AT pain. This finding also reaffirms the need to consider factors other than physical function in AT management. Another novel finding of this thesis was the association between COMT rs4818 (C/G) and chronic tendon pain. This finding suggests that the catecholaminergic pathway is involved in the chronic AT pain pathway. COMT variants are associated with maladaptive coping mechanisms which may be important to consider in managing chronic pain conditions such as AT. In future, larger studies are required in order to replicate these findings and large, prospective cohort studies are required to confirm the role of genetic variation in chronic AT pain. Overall, the mechanisms of pain in tendinopathy are complex and not yet well described, emphasising the further need for multi-sectorial research

Absolute and relative reliability of SCRuM test battery components assembled for schoolboy rugby players playing competitive rugby in low-resource settings: A pragmatic in-season test-retest approach

Background: Schoolboy rugby is a popular sport which forms the bedrock of rugby development in many African countries, including Zimbabwe. With burgeoning talent identification programmes, the development of multi-dimensional, logically- validated, and reliable test batteries is essential to inform the objective selection of potentially talented young rugby athletes. Objectives: This study sought evidence on the absolute and relative test-retest reliability of the component test items in the newly-assembled SCRuM test battery. Methods: Utilising a pragmatic test-retest experimental design, a sample of 41 Under-19 schoolboy players playing competitive rugby in the elite Super Eight Schools Rugby League in Harare, Zimbabwe, participated in the study. Results: Physiological and game-specific skills tests which showed good to excellent relative reliability and acceptable absolute reliability, included: 20 m and 40 m speed, L-run, Vertical Jump (VJ), 60 s Push-Up, 2 kg Medicine Ball Chest Throw test (2 kg MBCT), Wall Sit Leg Strength test (WSLS), Repeated High Intensity Exercise test (RHIE), One Repetition Maximum Back Squat (1-RM BS) and Bench Press tests (1-RM BP), Yo-Yo Intermittent Recovery Level 1 test (Yo-Yo IRT L1), Tackling Proficiency test, Passing Ability Skill test and Running and Catching Ability skill test. Conclusion: All these tests are reliable and warrant inclusion in the SCRuM test battery for possible profiling of U19 schoolboy rugby players during the ‘in-season’ phase provided there is adequate participant familiarisation and test standardisation. The test-retest ICCs and measurement errors are generalisable to other young athletes in this population, making the tests useful for the evaluation of training and developmental effects of the measured constructs

TENDINopathy Severity Assessment - Achilles (TENDINS-A):Development and Content Validity Assessment of a New Patient-Reported Outcome Measure for Achilles Tendinopathy

OBJECTIVE: To develop a new patient-reported outcome measure (PROM) assessing TENDINopathy Severity of the Achilles (TENDINS-Achilles) and evaluate its content validity. DESIGN: Mixed-methods, modified Delphi. METHODS: We performed 1 round of semistructured one-on-one interview responses with professionals and patients, for initial item generation. This was followed by 1 round of survey responses for professionals and a final round of semistructured one-on-one interviews with patients. The work culminated in a PROM to quantify Achilles tendinopathy severity under the core health domain of disability. Participants identified 3 subdomains contributing to the severity of disability of Achilles tendinopathy: pain, symptoms, and functional capacity. RESULTS: All 8 patient participants invited to participate were enrolled. Forty professional participants (50% women, six different continents) were invited to participate and 30 were enrolled (75% response rate). Therefore, a total of 30 professionals and 8 patients were included within this study. Following 3 rounds of qualitative or quantitative feedback, this study has established the content validity of TENDINS-A (good relevance, comprehensibility, and comprehensiveness) as a new PROM to assess the severity of Achilles tendinopathy, which assesses aspects of pain, symptoms, and functional capacity. CONCLUSION: TENDINS-A has established content validity and is appropriate for use with clinical and research populations. We recommend users interpret TENDINS-A results cautiously, until further testing evaluates the most appropriate scoring scale, reliability, construct validity, criterion validity, and responsiveness of TENDINS-A. Until these psychometric properties are established, we suggest using TENDINS-A alongside existing tools. J Orthop Sports Phys Ther 2023;53(11):1-16. Epub: 24 August 2023. doi:10.2519/jospt.2023.11964.</p

Minds matter : how COVID-19 highlighted a growing need to protect and promote athlete mental health

The Sports and Exercise Medicine community and other sport stakeholders are becoming increasingly aware of the mental health symptoms (eg, depression, anxiety, substance misuse) reported by athletes. In 2019, this led to the publication of the first International Olympic Committee (IOC) consensus statement on mental health in this cohort and the establishment of the IOC Mental Health Working Group.1 Over the past 2 years, the COVID-19 pandemic and related public health measures have presented additional challenges to the well-being of all populations, including athletes. This editorial reflects on how the COVID-19 pandemic has highlighted a growing need to protect and promote athlete mental health.http://bjsm.bmj.comhj2022Sports Medicin

Female athlete health domains:A supplement to the International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport

The IOC made recommendations for recording and reporting epidemiological data on injuries and illness in sports in 2020, but with little, if any, focus on female athletes. Therefore, the aims of this supplement to the IOC consensus statement are to (i) propose a taxonomy for categorisation of female athlete health problems across the lifespan; (ii) make recommendations for data capture to inform consistent recording and reporting of symptoms, injuries, illnesses and other health outcomes in sports injury epidemiology and (iii) make recommendations for specifications when applying the Strengthening the Reporting of Observational Studies in Epidemiology-Sport Injury and Illness Surveillance (STROBE-SIIS) to female athlete health data. In May 2021, five researchers and clinicians with expertise in sports medicine, epidemiology and female athlete health convened to form a consensus working group, which identified key themes. Twenty additional experts were invited and an iterative process involving all authors was then used to extend the IOC consensus statement, to include issues which affect female athletes. Ten domains of female health for categorising health problems according to biological, life stage or environmental factors that affect females in sport were identified: menstrual and gynaecological health; preconception and assisted reproduction; pregnancy; postpartum; menopause; breast health; pelvic floor health; breast feeding, parenting and caregiving; mental health and sport environments. This paper extends the IOC consensus statement to include 10 domains of female health, which may affect female athletes across the lifespan, from adolescence through young adulthood, to mid-age and older age. Our recommendations for data capture relating to female athlete population characteristics, and injuries, illnesses and other health consequences, will improve the quality of epidemiological studies, to inform better injury and illness prevention strategies

Genetic Variation as a Possible Explanation for the Heterogeneity of Pain in Tendinopathy: What can we learn from other pain syndromes?

The mechanisms of pain in tendinopathy are unclear. Current theories implicate tendon structural changes, neovascularisation, inflammation or changes in central pain processing. As with other types of musculoskeletal pain, tendon pain has high interindividual variability and, as with other types of pain, this could be attributed to genetic variation. Notably, the association between certain genetic polymorphisms and susceptibility to tendinopathy is well established in the literature. Therefore, the investigation of the mechanisms of tendon pain should also extend to include genetic variation as a possible explanation for the clinical features of tendon pain. This review summarises the current knowledge on genetic contributors to chronic pain and highlights findings that are relevant to chronic tendon pain. In particular, based on the current hypotheses on the possible sources of tendon pain, it focuses on findings that relate to genes that encode structural connective tissue components, inflammatory markers, ion channels and catecholamines and how they may relate to chronic tendon pain. In the absence of a definitive mechanism of tendon pain, an a priori genetic approach that is guided by these current hypotheses may help elucidate the mechanisms of tendon pain which may allow a more rational approach to research and treatment

Anthropometric and physical performance characteristics in African women football players: A prospective, cross-sectional pilot study

Being injured is inherent to participating in football activities; therefore, prevention of injuries is crucial. This requires that the risk factors for injury be established. However, such studies are rarely conducted in women athletes in Africa. The study’s aim was to explore intrinsic risk factors for injury among African women football players using functional and musculoskeletal assessments. Participants (n=40) completed demographic questionnaires; upper and lower limb active range of motion (AROM); muscle endurance and functional movement screening (FMS™) assessed. Median age [Q1; Q3] was 24 [20; 27] years. Participants performed 20.5 [0; 30.5] push-ups and 28 squats [30; 38] in 60s; and held the prone elbow plank for 46.2s [30.6; 64.5]. Median FMS™ score was 12 [10; 13]; most players (n=27, 68%) could not execute a proper deep squat. Most players (70%; n=28), were able to properly perform the in line lunge but scored poorly in the shoulder mobility domain of the FMS™, with 73% (n=29) scoring ≤1. Players with a history of injury had lower FMS™ total (p=0.02). Overall, participants presented with low muscle endurance and movement imbalances, which might predispose them to injury. Hence, strength and conditioning measures should be instituted in this population to prevent injuries

Knowledge, Attitudes, and Behaviors Toward the Menstrual Cycle and Menstruation Among Elite African Women Football Players, Coaches, Health Personnel, and Referees

Despite cross-cultural differences in knowledge and attitudes toward menstruation, most studies on menstruation in women’s sport have been conducted in high-income countries, such as in Europe, and none have been conducted in Africa. The aim of this study was to explore the knowledge, attitudes, and behaviors of African elite women football players, and their support personnel toward the menstrual cycle and menstruation. An anonymous questionnaire was distributed to all participants (n = 564) at two African women football tournaments. Ultimately, 238 women football players, 44 coaches, 18 health personnel, and 17 referees completed it. From 317 questionnaires analyzed, 17%, 27%, 56%, and 0% of players, coaches, health personnel, and referees, respectively, knew at least one menstrual cycle hormone; 91%, 95%, and 100% of players, coaches, and referees, respectively, did not know at least one menstrual cycle phase. Over 70% of health personnel believed that menstruation negatively affects women’s performance in sports compared with 36% of players; 18%, 28%, and 18% of players, health personnel, and referees, respectively, believed that, for convenience, the menstrual cycle should be changed by drugs like contraceptives; and 54%, 61%, 62%, and 40% of players, coaches, health personnel, and referees, respectively, were confident providing advice about the menstrual cycle to teammates. Minimal knowledge of the menstrual cycle has implications on the development of menstrual cycle considerate training environments and educational materials in African women’s football. Furthermore, the relatively low perceived effect of the menstrual cycle on sporting performance and belief in the use of contraceptives may be attributable to differences in communitylevel religiocultural and social contexts which influence menstrual experiences, and shape behavioral expectations

Conditioned pain modulation does not differ between people with lower-limb tendinopathy and non-tendinopathy controls:a systematic review with individual participant data meta-analysis

OBJECTIVE: To explore whether people with lower-limb tendinopathy have reduced relative conditioned pain modulation (CPM) when compared to nontendinopathy controls. DESIGN: Systematic review with individual participant data (IPD) meta-analysis. LITERATURE SEARCH: Eight databases were searched until August 29, 2022. STUDY SELECTION CRITERIA: Cross-sectional studies comparing the magnitude of the CPM effect in people with lower-limb tendinopathy to nontendinopathy controls in a case-control design. DATA SYNTHESIS: Included studies provided IPD, which was reported using descriptive statistics. Generalized estimating equations (GEEs) determined between-group differences in the relative CPM effect, when adjusting for co-variables. Study quality was assessed using a Joanna Briggs Institute checklist, and certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluations. RESULTS: Five records were included, IPD were provided for 4 studies (n = 219 with tendinopathy, n = 226 controls). The principal GEE (model 1) found no significant relative CPM effects for tendinopathy versus controls (B = -1.73, P = .481). Sex (B = 4.11, P = .160), age (B = -0.20, P = .109), and body mass index (B = 0.28, P = .442) did not influence relative CPM effect. The Achilles region had a reduced CPM effect (B = -22.01, P = .009). In model 2 (adjusting for temperature), temperature (B = -2.86, P = .035) and female sex (B = 21.01, P = .047) were associated with the size of the relative CPM effect. All studies were low-quality, and the certainty of the evidence was moderate. CONCLUSION: There were no between-group differences in the magnitude of the CPM effect, suggesting clinicians should manage lower-limb tendinopathy using interventions appropriate for peripherally dominant pain (eg, tendon loading exercises such as heavy slow resistance). Based on the "moderate"-certainty evidence, future studies are unlikely to substantially change these findings. J Orthop Sports Phys Ther 2023;54(1):1-10. Epub 19 October 2023. doi:10.2519/jospt.2023.11940. </p