Browsing by Author "Posthumus, Michael"

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    A randomised control trial for the restoration of functional ability in patients post total knee arthroplasty: Eccentric versus concentric cycling ergometry
    (2018) Silal, Sandhya Prakash; Albertus, Yumna; Tam, Nicholas; Posthumus, Michael
    Introduction: While the total knee arthroplasty procedure improves joint-specific outcomes, including pain and range of movement, functional deficits post-surgery has been noted. Movement abnormalities and quadriceps weakness of the operated limb, as well as a decrease in strength on the non-operated have been widely reported. Recovery of strength and function to normal levels is also rare, thereby predisposing patients to future disability with increasing age. The purpose of this study was to determine the effects of an eight-week eccentric cycling ergometry exercise intervention versus a concentric cycling ergometry exercise intervention in total knee arthroplasty recipients three to nine months post-surgery. This study aimed to a) investigate the change in joint kinetics, kinematics and muscle activity during the phases of gait, between the eccentric and concentric groups over time and b) To determine if an eccentric cycling exercise intervention produces greater improvements in knee function when compared to concentric cycling exercise. Methods: Eighteen participants, three to nine months post total knee arthroplasty were recruited and randomly assigned to either an eccentric or concentric cycling exercise intervention group. Participants performed three exercise sessions weekly over a progressive eight-week period on the Grucox Isokinetic Ergometer. Walking gait analyses and functional outcomes, as measured by the six-minute walk test and validated knee scores (Knee Injury and Osteoarthritis Outcome Score, SF-36 Health Survey and Tegner Activity Scale) were recorded pre- and post-intervention. Results: The concentric group knee flexion range of movement increased significantly during the swing phase of gait (p=0.021) post-intervention together with a significant increase in the peak knee flexion angle during swing (p=0.038). The concentric group showed significant differences between pre and post-rehabilitation in knee flexion range of movement during the swing phase of gait (p=0.030). Significant correlations between knee joint stiffness and the quadriceps:hamstring co-activation ratio were observed in the concentric intervention group pre-intervention: during the pre-activation phase of gait between knee joint stiffness and vastus medialis / biceps femoris (r=-0.68; p=0.042) and during load acceptance phase of gait between knee joint stiffness and vastus lateralis / biceps femoris (r=0.07; p=0.036). The eccentric group recorded neuromuscular changes post-intervention with a significant decrease in the muscle activity of the biceps femoris during load acceptance phase of gait (p=0.021). The eccentric group had significantly better functional outcomes in the overall score of Knee injury and Osteoarthritis Outcome post-intervention (p=0.008) with a significant increase in function seen in the Sports and Recreation subgroup (p=0.008) and a significant increase in the level of activity as measure by the Tegner Activity Scale post-intervention (p=0.028), despite not showing any significant changes in the knee joint kinetics and kinematics. The concentric group only reported a significant increase in the overall score of the of the SF-36 Health Survey (p=0.011) with significant increases in three of the subgroups post-intervention: Bodily pains had improved (p=0.042), the role limitations due to physical heath had improved (p=0.028) and the role limitations due to emotional health had also improved (p=0.009). The concentric group also showed significant improvement in the emotional health over the intervention in comparison to the eccentric intervention group (p=0.020). Both intervention groups reported a similar significant increase in the distance covered during the six-minute walk test post-intervention (p=0.038). Conclusion: The results of this exploratory study did not find the eccentric cycling rehabilitation intervention exclusively more effective than the concentric cycling intervention in the restoration of functional ability in patients post-TKA. The eccentric intervention did however result in neuromuscular adaptations consistent with a move towards a more typical asymptomatic gait pattern and participants reported greater functional improvements on validated knee functional assessments and levels of activity scores. The concentric intervention yielded kinematic changes and participants reported improvements in their emotional and physical health post-intervention. Eccentric training and its role in early stage post-operative rehabilitation is limited. Based on the findings from this exploratory study, the benefit of eccentric training as an adjunct to rehabilitation and its role in contributing to greater improvements in the restoration of functional ability post-TKA needs to be further explored.
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    Genetic risk factors for anterior cruciate ligament ruptures
    (2009) Posthumus, Michael; Collins, Malcolm; Schwellnus, Martin
    The primary aim of this thesis was to identify candidate genes that may be associated with ACL ruptures, and then use a genetic association approach following a case-control study design to identify specific sequence variants (single nucleotide polymorphisms, SNPs) within these candidate genes which may predispose individuals to ACL ruptures. Candidate genes (COL1A1, COL5A1 and COL12A1) were selected based on the biological function of their encoded proteins (type I, type V and type XII collagen respectively) within the basic structural and functional unit of ligaments, namely the collagen microfibril.
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    Genetic risk factors for overuse and acute musculoskeletal injuries
    (2024) Hill, Lee-Devlin; Collins, Malcolm; Posthumus, Michael
    Both acute and chronic tendon and ligament injuries are multifactorial that are the result of a combination of a poorly understood complex interaction of several intrinsic and extrinsic risk factors. There is a growing body of evidence suggesting that inherited genetic elements may predispose an individual to injury risk and should therefore be considered as important intrinsic risk factors. Previous studies have investigated the association several collagen gene (COL1A1, COL5A1, COL6A1, COL11A1, COL11A2 and COL12A1) variants with chronic lower limb tendinopathies, such as Achilles tendinopathy, and other exercise-associated phenotypes involving the musculoskeletal system. These genes encode for important structural components of both tendons and ligaments and have been proposed to influence the inter-individual variation in the biomechanical properties of these tissues. The association of these collagen gene variants with rotator cuff tendinopathy (RCT), more specifically supraspinatus tendinopathy (SST), has not been extensively investigated. Except for COL1A1 variants, the association of the remaining collagen gene variants with an acute injury, such as anterior cruciate ligament (ACL) ruptures, has also not been extensively investigated. AIMS Therefore, the primary aim of this thesis was to investigate the association of the COL1A1 rs1800012 (G/T), COL5A1 rs12722 (T/C), COL5A1 rs10628678 (AGGG/-), COL6A1 rs35796750 (T/C), COL11A1 rs3753841 (T/C), COL11A1 rs1676486 (C/T), COL11A2 rs1799907 (A/T) and COL12A1 rs970547 (G/A) gene variants with RCT in a South African cohort of swimmers (Chapter 4), as well as ACL rupture in a combined cohort of European ancestry (Swedish, South African, Polish and Australian) (Chapter 5) and a South African Mixed Ancestry cohort (Chapter 6) using a case-control genetic association study approach. A secondary aim of the thesis was to investigate hypothesis-driven collagen gene-gene interactions between the investigated variants in modulating the risk of injury in the different RCT (Chapter 4) and ACL (Chapters 5 and 6) cohorts. Finally, a systematic review of the risk factors associated with RCT in swimmers was also included in this thesis (Chapter 3). METHODS For chapter 4, 103 (49 females, 54 males) swimmers with clinically diagnosed rotator cuff tendinopathy (RCT group) were recruited of the 103 participants in the RCT group, 84.5% (n=87) were diagnosed with a supraspinatus tendinopathy (SST) and were analysed separately as a sub-group. In addition, 101 (55 females,46 males) apparently healthy swimmers with no previous history of shoulder pathology (including RCT, trauma, bursitis, or adhesive capsulitis) (CON group) were recruited. All participants were unrelated, of self-reported European ancestry and recruited between 2013 and 2016. For Chapter 5, 195 physically active and unrelated participants of self-reported European ancestry were recruited between 2011 and 2013 from the University Hospital in Umeå and orthopaedic clinics in Luleå, Sweden. These participants within this cohort comprised of 79 individuals who had clinically diagnosed ACL injuries with a non-contact mechanism of rupture (NON group) and 116 apparently healthy, asymptomatic individuals with no history of ACL injuries (CON group). The Swedish cohort was included in a larger combined analysis consisting of 661 participants with ACL rupture and 378 uninjured controls from previously published cohorts of self-reported European ancestry from South Africa, Poland, and Australia. For chapter 6, 209 unrelated participants with self-reported mixed ancestry participants were included in this study. The participants were previously recruited between January 2012 and May 2016 from Groote Schuur Hospital, Victoria Hospital, and the Sports Science Orthopaedic Clinic within the Cape Town, South Africa. Ninety-four participants (77 males and 17 females) were included in the ACL group, of which 51 had sustained their ACL rupture through a non contact mechanism of injury (NON sub-group. Furthermore, 100 (81 males and 19 females) apparently healthy, individuals with no history of ACL rupture or injury were recruited from gyms and local sports clubs within the Cape Town area of South Africa. All participants were genotyped for the following collagen gene polymorphisms: COL1A1 rs1800012 (G/T), COL5A1 rs12722 (T/C) and rs10628678 (AGGG/-), COL6A1 rs35796750 (T/C), COL11A1 rs3753841 (T/C) and rs1676486 (C/T), COL11A2 rs1799907 (A/T) and COL12A1 rs970547 (G/A). RESULTS As presented in a systematic review of non-genetic risk factors (Chapter 3), only four risk factors for shoulder injuries were determined to be of moderate certainty, with the remaining 25 risk factors being appraised as low certainty. Moderate level of certainty was determined in (i) previous history of pain and injury, (ii) internal/external rotation range of motion, (iii) clinical joint laxity and instability and (iv) internal/external rotation strength. Although previously associated in some studies investigating other overuse musculoskeletal soft tissue injuries, none of the investigated collagen variants were independently associated with rotator cuff tendinopathy (RCT) or supraspinatus tendinopathy (SST) risk (Chapter 4). A novel finding of this thesis was that the C-A-(-) inferred haplotype constructed from COL11A1 rs3753841(T/C), COL11A2 rs1799907 (A/T) and COL5A1 rs10628678 (AGGG/-) was found to be significantly over-represented in the CON group (6.0 %) compared to the SST (0.4 %) groups (p=0.034). However, none of the inferred haplotypes constructed from (i) the two COL5A1 variants, (ii) the two COL11A1 variants, (iii) the three COL11A1 and COL11A2 variants, as well as all (iv) the COL11A1, COL11A2 and COL5A1 variants were associated with RCT or SST risk. Similarly inferred haplotypes constructed from (i) COL5A1 and COL6A1, (ii) COL5A1 and COL12A1, as well as (iii) COL6A1 and COL12A1 were also not associated with RCT or SST. The COL1A1 rs1800012 TT genotype was found to be significantly (p=0.027) under represented in the ACL (GG 68.0%, GT 30.9%, TT 1.1%) group of European ancestry during the combined analysis compared to the CON group (GG 67.0%, GT 29.0%, TT 4.0 %). A novel finding of this thesis was that this association was only observed in female (p = 0.045, OR = 0.00, CI 0.00 – 0.71; ACL: GG 68.1%, GT 31.9%, TT 0.0%; CON: GG 68.3%, GT 27.0%, TT 4.8%) but not male (p =0.299; ACL: GG 68.0%, GT 39.5%, TT 1.5%; CON: GG 66.5%, GT 31.0%, TT 3.6%) ACL groups. Although independently associated with ACL rupture in European populations, the COL1A1 rs1800012 TT genotype was however not significantly associated with ACL rupture in the Mixed Ancestry cohort (ACL: 85.4% GG, 13.5% GT and 1.0% TT vs CON: 82.3% GG, 17.7% GT and 0.0% GG, p=0.204). An additional novel finding was that the COL12A1 rs970547 polymorphism was significantly associated with risk in a South African Mixed Ancestry ACL rupture cohort (NON: 34.9% AA, 44.2% GA and 20.9% GG vs CON: 34.4% AA, 60.2% AG and 5.4% GG, p=0.021). This variant was however not associated with ACL rupture in the European populations (ACL: AA 63.7%, GA 31.3%, GG 5.1%) compared to the combined CON group (CON: AA 60.4%, GA 35.3%, GG 4.3%, p=0.423). None of the other investigated collagen gene variants were independently associated with ACL rupture in the European or mixed ancestry cohorts. Within participants of European ancestry, the C-AGGG (31.2% ACL vs 20.6% CON, p=0.001) and T-(-) (14.4% ACL vs 5.7% CON, p=0.010) inferred haplotypes constructed from COL5A1 rs12722 (C/T) and rs10628678 (AGGG/-) were significantly over-represented in the ACL rupture group. On the other hand the T-AGGG inferred haplotype was significantly (p>0.001) over-represented in the CON group (50.5%) compared to the ACL group (36.6%). None of the COL5A1 inferred haplotypes were however significantly associated with ACL rupture in the South African mixed ancestry cohort. A further novel finding was a significant interaction between the COL6A1 rs35796750 and COL12A1 rs970547 variants, the T-A inferred haplotype was significantly (p=0.030) over represented in the ACL group (11.0%) compared to the CON group (7.1%) when the participants of European ancestry were analysed. The T-G inferred haplotype was significantly (p=0.010) over-represented in the male CON sub-group (33.7%) compared to the male ACL sub group (23.0%) in the participants of European ancestry. Within the South African mixed ancestry population, the C-G inferred haplotype constructed from the COL6A1 and COL12A1 variants was significantly (p=0.029) over-represented in the ACL group (37.2%) compared to the CON group (31.1%). This haplotype remained significantly (p=0.027) associated when only the participants with a non-contact mechanism of injury (34.3% NON sub-group) was analysed. Finally, the inferred T-A haplotype constructed from COL5A1 rs12722 and COL12A1 rs970547 was significantly (p=0.039) with ACL rupture (27.3% ACL vs 17.9% CON) in the combined European cohort associated with risk. CONCLUSION This thesis investigated collagen gene variants that have been previously associated with a number of injury phenotypes and other exercise-related conditions in three independent cohorts. Whilst only two variant were found to be independently associated with risk, several gene-gene interactions were observed, demonstrating the complex and multifactorial nature of the MSK injuries. These novel findings therefore draw attention to the possible important role that genetic factors in the aetiology of tendon and ligament pathologies. Furthermore, this thesis highlights the importance of conducting studies in non-European and genetically diverse populations.
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    Investigation of selected collagen genes in exercise-related musculoskeletal soft tissue phenotypes
    (2014) O’Connell, Kevin Sean; Collins, Malcolm; Posthumus, Michael
    Previous findings have suggested that functional variants within collagen encoding genes are associated with several musculoskeletal soft tissue injuries and other exercise-related phenotypes. Specifically variants within the functional COL5A1 3’- untranslated region (UTR) have previously been associated with (1) chronic Achilles tendinopathy, (2) Anterior Cruciate Ligament (ACL) ruptures in females, (3) endurance running performance and (4) range of motion (ROM). Since this gene encodes for an important structural component of the collagen fibril it has been hypothesised that variants within other collagen fibril encoding genes, such as COL3A1, COL6A1 and COL12A1, will also be associated with these and/or other musculoskeletal soft tissue injuries and exercise-related phenotypes. The COL5A1 rs12722 and COL12A1 rs970547 gene variants have been previously associated with risk of ACL ruptures in females [153;154] and/or chronic Achilles tendinopathy [131;181]. The first aim of this thesis was therefore to investigate the COL3A1 rs1800255 and COL6A1 rs35796750 gene variants as risk factors for these musculoskeletal soft tissue injuries.
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    A randomised control trial for the restoration of functional ability in patients post total knee arthroplasty: a comparison of eccentric versus concentric cycling ergometry
    (2015) Bakkum, Amanda; Posthumus, Michael; Albertus, Yumna; Collins, Malcolm
    Purpose: The predominant impairment to function following a total knee arthroplasty (TKA) is a distinctive reduction in quadriceps muscle strength. It has been suggested that eccentric rehabilitation may be more beneficial than traditional concentric only rehabilitation at improving muscle strength, physical functioning and quality of life in this population. The aim of this study was therefore to determine if an eccentric cycling ergometry rehabilitation intervention (a) was feasible in participant's early after TKA surgery (Study 1), (b) resulted in greater improvements in muscle strength and endurance, as well as muscle activity and muscle volume (Study 2) and, (c)resulted in greater knee functional ability, health related quality of life and physical activity levels (Study 3), when compared to an concentric cycling ergometry rehabilitation intervention. Finally, knee and hip kinematics, ground reaction force and muscle activity was described during the sit-to-stand transfer within this population (Study 4). Methods: Eighteen age- and sex-matched participants', three to nine month's post-TKA were recruited and randomly divided into either an eccentric or concentric cycling rehabilitation intervention. The participants were required to perform three exercise sessions a week, over a period of eight weeks. Isokinetic strength and muscle activity of the quadriceps and hamstring muscles, sit-to-stand motion capture analysis and knee functional ability and health related quality of life questionnaires (Knee Injury and Osteoarthritis Outcome Score, SF-36Health Survey and Tegner Activity Scale) were assessed pre and post- rehabilitation intervention. Data Analysis: Two-way repeated-measures analysis of variance were used to analyse the effects of time and the ECC and CON intervention groups and the group/time interaction for each of the dependent variables. Results: The eccentric rehabilitation intervention was well tolerated with regards to pain levels in participants' as early as three months post-TKA, the peak level of pain perceived per session, never exceeding a "mild" classification. The eccentric intervention resulted in greater power (P= 0.029) and work output (P ≤ 0.001) with a reduced overall heart rate (P= 0.014) ; moderate decreases in biceps femoris (BF) muscle activity (-3.2%) and increases in the lean thigh volume (+807.32) of the uninvolved limb; as well as improvements in the physical fun ctioning (+12.2%) and physical role functioning SF-36 scores (+22.2%) and the level of physical activity (+0.9) (Tegner activity scale). The concentric intervention resulted in decreases in vastus lateralis (VL) muscle activity (-8.17%) and work fatigue (-7.34%) and increases in the lean thigh volume (+677.49) and the hip abduction angle (+ 2.67°) (sit-to-stand) of the involved limb. Conclusion: The eccentric rehabilitation intervention is well tolerated with regards to pain and is characterised by significantly greater power output produced and work performed at significantly lower heart rates. Eccentric cycling ergometry matched in perceived exertion and duration, is associated with greater improvements in physical functioning outcome scores, physical activity level and knee flexion muscle efficiency during concentric contractions, when compared with concentric cycling ergometry. However, knee extensor muscle endurance and efficiency during concentric contractions, as well as muscle volume of the involved limb increased more significantly after concentric training in comparison to eccentric training, Further research is required to establish which training modality is the most feasible and effective in restoring knee function in participant's three months post-TKA.
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    The aetiology of pain in chronic midportion Achilles tendinopathy
    (2021) Mkumbuzi, Nonhlanhla Sharon; Collins, Malcolm; September, Alison; Posthumus, Michael
    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 p<0.05. Results From the sf-MPQ, the most frequent descriptors in the sensory index were ‘aching' (n=73, 60.3%), ‘tender' (n=64, 52.9%) and ‘throbbing' (n=41, 33.9%). Words from the affective index of the sf-MPQ were seldom used to describe tendon pain. From the sf BPI, in addition to interfering with walking ability, AT pain also interfered with mood (n=61, 50.8%), sleep (n=40, 34.8%) and relationships with others (n=30, 25.0%). Additionally, there were weak to moderate correlations between corresponding indices on the sf-MPQ, VISA-A and sf-BPI (r2>0.3; p<0.05) and the VISA-A scores were lower when participants reported severe tenderness (p=0.005), sharp (p=0.030) and/or stabbing pain (p=0.048) on the sf-MPQ. On US and CD, the TEN participants had thicker tendons [median (IQR)] [TEN 6.3mm (5.4 - 7.9) vs CON 5.5mm (4.8 - 6.0), p<0,001]; relative abnormal ultrasound appearances (TEN 48.7%, n=38 vs CON 22.4%, n=19, p=0.001) and had more neovessels (TEN 20.5%, n=16 vs CON 1.0%, n=1, p=0.001) (p<0.001) than the CON participants. In the TEN group, no significant differences were noted between the self reported total pain scores of the sf-MPQ, sf-BPI and VISA-A scales or their separate indices and tendon diameter, US abnormalities or presence of neovessels (p>0.05). 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.
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    The COL5A1 gene and musculoskeletal soft-tissue injuries
    (2010) Posthumus, Michael; September, Alison V; Schwellnus, Martin P; Collins, Malcolm
    Background. It has been shown that there is an association between various genetic variants and Achilles tendon injuries as well as anterior cruciate ligament (ACL) ruptures. Among other variants the BstUI restriction fragment length polymorphism (RFLP) within the COL5A1 gene has been shown to be over-represented in asymptomatic participants when compared with those with chronic Achilles tendinopathy, and in asymptomatic female participants when compared with those with ACL ruptures. The male asymptomatic control participants in the ACL study, which were 10 years younger than previously investigated cohorts, had a distinctly different genotype frequency. Aim. The aim of this study was therefore to determine whether the distribution of the COL5A1 BstUI RFLP in the combined asymptomatic participants without any known history of tendon injuries is age dependent, particularly among males. Results. When the 265 male asymptomatic participants from all studies were pooled and divided into age-group tertiles, there was a significant linear increase in the CC genotype frequency (p=0.032) among the male age groups, with the youngest group having the lowest frequency (CC genotype frequency, 13%) and the oldest group having the highest (CC genotype frequency, 27%) frequency. There was however a similar CC genotype content in all three female (N=231) age groups (CC genotype frequency, 24 - 27%; p=0.795). Conclusion. The practical implication is that the selection of asymptomatic groups is of critical importance when future studies of this nature are designed. Future research investigating this genetic variant as a risk factor for soft-tissue injuries should consider these findings when selecting asymptomatic participants.