Tendinopathien der Achilles- oder Patellarsehne sind häufig in Sportarten mit zahlreichen repetitiven Belastungen im Dehnungs-Verkürzungs-Zyklus der unteren Extremität zu finden. Sowohl eine möglicherweise alterierte belastungsspezifische neuromuskuläre Antwort (NMA), als auch funktional begründete Therapiemaßnahmen mit möglichen positiven Effekten sind aktuell ungeklärt. Ziel der Arbeit war deshalb die Untersuchung der belastungsspezifischen neuromuskulären Antwort bei Athleten mit Tendinopathie der Achilles- oder Patellarsehne im Vergleich zu beschwerdefreien Athleten. Zusätzlich sollten mögliche funktionale und therapeutische Effekte eines sensomotorischen Trainings im randomisierten, kontrollierten und prospektiven Studiendesign überprüft werden. 51 Sportler mit unilateraler Tendinopathie (Achilles-/Patellarsehne n = 35/16) und 33 gesunde Sportler wurden zur Beurteilung der belastungsspezifischen neuromuskulären Antwort eingeschlossen. Zur Klärung der Effekte eines sensomotorischen Trainings im Längsschnitt konnten 26 Sportler mit Tendinopathie randomisiert zu einer Kontrollgruppe (n = 14) und einer Therapiegruppe mit sensomotorischem Training (n = 12) zugeordnet werden. Nach einer ersten biomechanischen Messung M1 (Belastungssituationen: Lauf-, Stabilisations-, Kraftbelastung) und der Erhebung der subjektiven Schmerzsymptomatik folgte eine 8-wöchige Therapiephase mit einer abschließenden Re-Test-Messung M2 identisch zu M1. Das sensomotorische Training war auf die gesamte untere Extremität ausgerichtet und wurde nach Einweisung regelmäßig kontrolliert. Die Erfassung der NMA erfolgte über die Quantifizierung der muskulären Aktivität (EMG). Zusätzlich wurde die Kinetik (z.B. Maximalkraft) belastungsspezifisch erfasst. Eine reduzierte NMA konnte für die Sportler mit Tendinopathie über veränderte EMG-Zeit- und Amplitudenmessgrößen, eine reduzierte aktive Stabilisationsfähigkeit und Maximalkraft (p < 0,05) nachgewiesen werden. In Abhängigkeit der Lokalisation (Achilles-/Patellarsehen) bzw. der Seite (Beschwerdeseite/gesunde Seite) ergaben sich keine relevanten Differenzen. Das sensomotorische Training zeigte eine Optimierung der NMA (z.B. erhöhte Maximalkraft) bei Tendinopathie der Achilles- oder Patellarsehne. Die Überprüfung der Beschwerdesymptomatik wies in allen Schmerz-Scores nach der Therapie reduzierte Werte und damit einen positiven therapeutischen Effekt gegenüber der Kontrollgruppe auf. Zusammenfassend kann eine systematisch reduzierte NMA bei Lauf-, Stabilisations- und Kraftbelastung der Sportler mit Tendinopathie nachgewiesen werden. Das sensomotorische Training ist funktional und therapeutisch als effiziente Therapiemaßnahme zu erachten. / Tendinopathies of the achilles- or patellartendon are common overuse unjuries in sports including high numbers of repetitive stretch-shortening-cycles of the lower limb. Possible alterations of the neuromuscular response (NMR) to physical stress and functionally justified therapies with potential positive effects are currently unknown. The aim of the study was therefore the analysis of the neuromuscular response in situations with physical stress in athletes with tendinopathie of the achilles or patellartendon compared to symptom free athletes. In addition, possible functional and therapeutic effects of a sensorimotor training were studied in a prospective, randomized and controlled study. 51 athletes with unilateral tendinopathy (achilles-/patellartendon n = 35/16) and 33 healthy athletes were included to assess the stress related neuromuscular response (NMR). To clarify the effects of a sensorimotor training 26 athletes with tendinopathy were randomized to a control group (n = 14) and a therapy group with sensorimotor training (n = 12). After initial biomechanical measurements M1 (situations: running, active postural stability and maximum strength test) and the collection of subjective complaints (pain) an 8-week treatment phase followed with a final re-test M2 measure identical to M1. The sensorimotor training was arranged for the entire lower extremity, and was checked after an initial briefing on a regular basis. The assessment of the NMR was quantified by muscle activity (EMG). In addition, the kinetics (e.g. maximum force) was acquired in the stabilization and maximum strength test. A reduced NMR could be proven for athletes with tendinopathy with changed EMG time and amplitude measurements, a reduced active postural stabilization ability and reduced maximum strength (p <0.05). No relevant differences could be observed in comparing localization (achilles-/patellartendon) and side (leg with complains/healthy leg). The sensorimotor training showed an optimization of NMR (e.g. increased maximum strength) for patient with tendinopathy of the achilles- or patellartendon. The examination of the complaints showed reduced values in all pain scores after therapy. The treatment had therefore positive therapeutic effects compared to the control group. In summary, a systematically reduced NMR in running, stabilization and strength tests are evident for athletes with tendinopathy. The sensorimotor training can be considered as an efficient treatment with functional and therapeutic effects.

The principal aim of the present thesis was to prospectively follow (clinical status and ultrasound + Doppler findings) the patellar tendons in the young elite volleyball players at the Swedish National Centre for high school volleyball in Falköping. In an Olympic weightlifter with chronic painful jumper´s knee, the effects of treatment with sclerosing injections followed by early instituted very heavy weightlifting training, was also evaluated. First, in a prevalence study, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee, together with structural tendon changes and vascularisation in the painful area of the tendon, was demonstrated in 12/114 tendons in Swedish junior elite volleyball players, but not in any tendons of individually matched (age, height and weight) not regularly sports active controls. Structural tendon changes alone was demonstrated among the volleyball players but also among the controls. In a 7 months prospective study of a total of 120 tendons, we demonstrated that the clinical diagnosis patellar tendinopathy-jumper’s knee was associated with neovessels/vascularity in the area with structural tendon changes in 17/19 tendons. Seventy tendons that at start were clinically normal, and had normal ultrasound + Doppler findings, remained clinically normal after 7 months with intensive training and playing volleyball. In a 3-year prospective study it was demonstrated that normal clinical tests and normal ultrasound + Doppler findings at school start, indicated a low risk (8%) for these players to sustain patellar tendinopathy-jumper’s knee during the 3 school years with intensive training and playing. In a case study, involving an Olympic elite weightlifter with chronic painful patellar tendinopathy-jumper’s knee, successful treatment with ultrasound and Doppler-guided injection of the sclerosing agent polidocanol, allowed for pain-free very heavy weight training two weeks after treatment. Further heavy weightlifting training on a daily basis, preparing for European Championships, was done without causing tendon rupture and/or pain. Key words: Jumper’s knee, Patellar tendinopathy, Chronic pain, Ultrasonography, Doppler, Neovascularisation, Volleyball, Weightlifting

Tendinopathies are painful tendon conditions of presumably multifactorial genesis. In tendinosis, as in Achilles tendinosis, there is apart from pain also morphological changes which are described as degenerative with no signs of inflammation. The exact mechanisms behind these conditions are still, to a large extent, unknown. Pain, being the foremost impairing symptom, leads us to the hypothesis that nerves are deeply involved in the symptoms and processes of Achilles tendinosis. Locally produced nerve signal substances may also be involved in the processes. Knowledge of the innervation patterns within the tendon and knowledge on a possible local nerve signal substance production are therefore of utmost importance. There is a lack of information on these aspects. The specific aims of this thesis were 1) to investigate the innervation patterns regarding general, sensory, cholinergic and sympathetic innervations, and 2) to examine for the possible occurrence of a production of nerve signal substances and a presence of receptors related to these in the tendon cells, the tenocytes. Painfree normal and tendinosis Achilles tendons were examined. Immunohistochemistry, using antibodies against the general nerve marker PGP9.5, the synthesizing enzymes for acetylcholine (choline acetyltransferase; ChAT), and catecholamines (tyrosine hydroxylase; TH), the vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), substance P and calcitonin gene-related peptide, was applied. Immunohistochemistry was also used for the delineation of muscarinic (M2R), adrenergic (α1-AR) and NPY-ergic (Y1 and Y2) receptors. To detect mRNA for TH and ChAT, in situ hybridization was used. In normal Achilles tendons, as well as in the tendinosis tendons, there was a very scanty innervation within the tendon tissue proper, the main general, sensory and sympathetic innervations being found in the paratendinous loose connective tissue. Interestingly, the tenocytes showed immunoreactions for ChAT, VAChT, TH, M2R, α1-AR and Y1R. The reactions were clearly more observable in tendons of tendinosis patients than in those of controls. The tenocytes of tendinosis patients also displayed mRNA reactions for ChAT and TH. Nevertheless, all tenocytes in the tendinosis specimens did not show these reactions. Immunoreactions for α1-AR, M2R and Y1R were also seen for blood vessel walls. The present thesis shows that there is a very limited innervation within tendon tissue proper, whilst there is a substantial innervation in the paratendinous loose connective tissue. It also gives evidence for an occurrence of production of catecholamines and acetylcholine in tenocytes, especially for tendinosis tendons. Furthermore, that ACh, catecholamines and NPY can have effects on these, as well as on blood vessels, via the receptors observed. The observations suggest that Achilles tendon tissue, whilst containing a very scarce innervation, exhibits autocrine/paracrine cholinergic/catecholaminergic/NPY-ergic effects that are upregulated in tendinosis. These findings are of great importance as the results of such effects may mimic processes that are known to occur in tendinosis. That includes effects related to proliferation and angiogenesis, and blood vessel and collagen regulating effects. In conclusion, within the Achilles tendon there is a very scarce innervation, whilst there appears to be a marked local production of nerve signal substances in Achilles tendinosis, namely in the tenocytes, the cells also harbouring receptors for these substances. The observations give a new insight into how the tendon tissue of the Achilles tendon is influenced by signal substances and may give options for new treatments of Achilles tendinosis.

Tendinosis is a condition of chronic pain that afflicts several human tendons, not least the patellar tendon, in which case it is often clinically referred to as ‘jumper’s knee’. The exact mechanisms behind tendinosis are yet not fully understood. One draw-back in the case of patellar tendinosis has been the lack of knowledge of the innervation patterns of the human patellar tendon. It cannot be excluded that the processes of tendinosis are influenced by nerve mediators, released from nerve endings or from stimulated cells inside the tendon. Thus, the studies of the present thesis aimed to 1) map the general, sensory, cholinergic and sympathetic innervation patterns of the human patellar tendon, in both the tendon tissue proper and the loose paratendinous connective tissue surrounding the tendon, and 2) investigate the possible existence of a production of signal substances, traditionally associated with neurons, in non-neuronal tendon cells, and to see if there are signs of local cholinergic and catecholaminergic signaling pathways. Biopsies of both normal pain-free patellar tendons and patellar tendons from patients with chronic painful tendinosis were collected and investigated. The main method utilized was immunohistochemistry, using antibodies directed against synthesizing enzymes for acetylcholine and catecholamines, against muscarinic and adrenergic receptors, and against markers of general and sensory innervation. In situ hybridization (ISH) to detect mRNA for the cholinergic/catecholaminergic synthesizing enzymes was also used. It was found that the loose paratendinous connective tissue of the patellar tendon was rather richly innervated by nerve structures. These consisted of large nerve fascicles, as well as perivascular innervation in the walls of some of the larger arteries and smaller blood vessels. It was found that part of the nerve structures corresponded to sensory afferents, and that some conformed to cholinergic and, especially, sympathetic nerve fibers. The tendon tissue proper was strikingly less innervated than the paratendinous tissue. The sparse innervation that was found in the tendon tissue proper was seen in narrow zones of loose connective tissue and blood vessels, interspersed between the collagen bundles. The overall impression was that the patterns of distribution of the general, sensory, and autonomic innervations of tendinosis tendon tissue were similar to those of normal tendon tissue proper. The most pioneering findings were the immunohistochemical observations of an expression of enzymes related to production of both acetylcholine and catecholamines within the tendon cells (tenocytes) themselves, as well as of a presence of the receptors for these substances on the same cells; features that were predominantly seen in tendinosis tendons. The observations of the synthesizing enzymes for acetylcholine and catecholamines in tenocytes were confirmed by ISH findings of mRNA for these enzymes in the tenocytes. Immunoreactions for muscarinic and adrenergic receptors were also found in blood vessel walls and in some of the nerve fascicles. In summary, this thesis presents novel information on the innervation patterns of the human patellar tendon, in healthy individuals with pain-free tendons as well as in patients with chronic painful tendinosis. Furthermore, it gives the first evidence of the presence of a local, non-neuronal production in the tendon tissue of signal substances normally seen in neurons, and a basis for these substances to affect the tenocytes as these cells also display muscarinic and adrenergic receptors. Thus, the results indicate an existence of autocrine and/or paracrine cholinergic/catecholaminergic systems in the tendon tissue; systems that seem to be up-regulated in tendinosis. This is of great interest as it is known that stimulation of receptors for both catecholamines and acetylcholine can lead to cell proliferation, interfere with pain sensation, influence collagen production, and take part in vasoregulation, as well as, in the case of adrenergic receptors, promote cell degeneration and apotosis. All these processes represent biological functions/events that are reported to be affected in tendinosis. In conclusion, despite the fact that there is very limited innervation within the patellar tendon tissue proper, it is here shown that effects of signal substances traditionally associated with neurons seem to occur in the tissue, via a local production of these substances in tenocytes.

Chronic painful tendinopathies are common, not only in sports and recreationally active people, but also among people with a sedentary lifestyle. Both the lower and upper limbs are affected. There is lack of knowledge about the etiology and pathogenesis to tendinopathy, and many different treatments options have been presented. Unfortunately, most treatments have not been tested in scientific studies. Conservative (non-surgical) treatment has since long shown unsatisfactory results and surgical treatment is known to give unpredictable results. The aim of this thesis was to evaluate new models of painful eccentric training for the conservative treatment of different chronic tendinopathies. After promising results in a pilot study, using painful eccentric calf muscle training in patients with chronic mid-portion Achilles tendinopathy, we investigated if these results could be reproduced in a larger group of patients with both mid-portion and insertional Achilles tendinopathy (study I). After 12 weeks, 89% of the patients with pain from the mid-portion were satisfied and back in previous activities. In the group with insertional Achilles tendinopathy the results were poor. A new model for eccentric training was designed for patients with insertional Achilles tendinopathy. The eccentric calf muscle training was done from tip-toe to floor level (study II). With this new regimen 67% of the patients were satisfied and back in previous activities. The next step was to investigate the effects of painful eccentric quadriceps training on patients with jumper´s knee/patellar tendinopathy (study III). Two different training protocols were used. Eccentric training performed on a 250 decline board showed promising results with reduced pain and a return to previous activities, while eccentric training without the decline board had poor results. In a following prospective study, patients with jumper´s knee/patellar tendinopathy were randomised to either concentric or eccentric painful quadriceps training on a 250 decline board (study IV). After 12 weeks of training, there were significantly better results in the group that did eccentric training. In a pilot study (study V), we investigated painful eccentric deltoideus and supraspinatus muscle training on a small group of patients on the waiting list for surgical treatment of subacromial impingement syndrome. After 12 weeks of training, 5 out of 9 patients were satisfied with the results of treatment and withdrew from the waiting list for surgery. In conclusion, the present studies showed good clinical results with low risks of side effects and low costs. Thus, we suggest that painful eccentric training should be tried in patients with Achilles and patellar tendinopathy before intratendinous injections and surgery are considered. For patients with chronic painful impingement syndrome, the results of our small pilot study are interesting, and stimulates to randomised studies on larger materials.

Pain of the musculoskeletal system is one of the most common reasons for people seeking medical attention, and is also one of the major factors that prevent patients from working. Chronic tendon pain, tendinopathy, affects millions of workers world-wide, and the Achilles tendon is an important structure often afflicted by this condition. The pathogenesis of tendinopathy is poorly understood, but it is thought to be of multifactoral aetiology. It is known that tendon pain is often accompanied not only by impaired function but also by structural tissue changes, like vascular proliferation, irregular collagen organisation, and hypercellularity, whereby the condition is called tendinosis. In light of the poor knowledge of tendinosis pathophysiology and recent findings of a non-neuronal signalling system in tendon tissue, the contributory role of neuropeptides such as substance P (SP) has gained increased interest. SP, known for afferent pain signalling in the nervous system, also has multiple efferent functions and has been described to be expressed by non-neuronal cells. As pain is the most prominent symptom of tendinopathy, the focus of the studies in this thesis was the innervation patterns of the tissue ventral to the Achilles tendon (i.e. the tissue targeted in many contemporary treatment methods) as well as the distribution of SP and its preferred receptor, the neurokinin-1 receptor (NK-1R), in the tendon tissue itself. It was hereby hypothesised that the source of SP affecting the Achilles tendon might be the main cells of the tendon tissue (the tenocytes) as well as paratendinous nerves, and that SP might be involved in tendinosis- development. The studies were conducted, via morphological staining methods including immunohistochemistry and in situ hybridisation, on tendon biopsies from patients suffering from Achilles tendinosis and on those from healthy volunteers. The hypothesis of the thesis was furthermore tested using an experimental animal model (rabbit) of Achilles tendinopathy, which was first validated. The model was based on a previously established overuse protocol of repetitive exercise. In the human biopsies of the tissue ventral to the Achilles tendon, there was a marked occurrence of sympathetic innervation, but also sensory, SP-containing, nerve fibres. NK-1R was expressed on blood vessels and nerve fascicles of the paratendinous tissue, but also on the tenocytes of the tendon tissue proper itself, and notably more so in patients suffering from tendinosis. Furthermore, the human tenocytes displayed not only NK-1R mRNA but also mRNA for SP. The animal model was shown to produce objectively verified tendinosis-like changes, such as hypercellularity and increased vascularity, in the rabbit Achilles tendons, after a minimum of three weeks of the exercise protocol. The contralateral leg of the animals in the model was found to be an unreliable control, as bilateral changes occured. The model furthermore demonstrated that exogenously administered SP triggers an inflammatory response in the paratendinous tissue and accelerates the intratendinous tendinosis-like changes such that they now occur after only one week of the protocol. Injections of saline as a control showed similar results as SP concerning hypercellularity, but did not lead to vascular changes or pronounced paratendinous inflammation. In summary, this thesis concludes that interactions between the peripheral sympathetic and sensory nervous systems may occur in Achilles tendinosis at the level of the ventral paratendinous tissue, a region thought to be of great importance in chronic tendon pain since many successful treatments are directed toward it. Furthermore, the distribution of NK-1R:s in the Achilles tendon described in these studies gives a basis for SP, whether produced by nerves mainly outside the tendon or by tenocytes within the tendon, to affect blood vessels, nerve structures, and/or tendon cells, especially in tendinosis patients. In light of this and of previously known SP-effects, such as stimulation of angiogenesis, pain signalling, and cell proliferation, the proposed involvement of SP in tendinosis development seems likely. Indeed, the animal model of Achilles tendon overuse confirms that SP does induce vascular proliferation and hypercellularity in tendon tissue, thus strengthening theories of SP playing a role in tendinosis pathology.

Background: Achilles tendinopathy is a common clinical syndrome of chronic Achilles tendon pain combined with thickening of the tendon and impaired tendon function. Tendinopathy is often, but not always, induced by mechanical overload, and is frequently accompanied by abnormalities at the tissue level, such as hypercellularity and angiogenesis, in which case the condition is called tendinosis. In tendinosis, there are no signs of intratendinous inflammation, but occasionally increased apoptosis is observed. Tendinosis is often hard to treat and its pathogenesis is still not clear. Recently, a new hypothesis has gained support, suggesting a biochemical model based on the presence of a non-neuronal production of classically neuronal signal substances by the primary tendon cells (tenocytes) in tendinosis. The possible functional importance of these signal substances in tendons is unknown and needs to be studied. In particular, the neuropeptide substance P (SP) and catecholamines are of interest in this regard, since these substances have been found to be up-regulated in tendinosis. As both SP and catecholamines are known to exert effects in other tissues resulting in changes similar to those characteristic of tendinosis, it is possible that they have a role in tendinosis development. It is furthermore unknown what elicits the increased intratendinous neuropeptide production in tendinosis, but given that tendon overload is a prominent riskfactor, it is possible that mechanical stimuli are involved. The hypothesis of this thesis work was that intratendinous production of SP is up-regulated in response to load of Achilles tendons/tenocytes, and thatstimulation of the preferred SP receptor, the neurokinin-1 receptor (NK-1 R), aswell as stimulation of the catecholamine α2 adrenoreceptors, contribute to the hypercellularity seen in tendinosis, via increased proliferation and/or decreased apoptosis, and that SP stimulates tendon angiogenesis. The purpose of the studies was to test this hypothesis. To achieve this, two model systems were used: One in vivo (rabbit Achilles tendon overload model of tendinosis) and one in vitro (human primary Achilles tendon cell culture model). Results: In the rabbit Achilles tendon tissue, SP and NK-1 R expression was extensive in the blood vessel walls, but also to some extent seen in the tenocytes. Quantification of endogenously produced SP in vivo confirmed intratendinous production of the peptide. The production of SP by human tendon cells in vitro was furthermore demonstrated. The catecholamine synthesizing enzyme tyrosine hydroxylase (TH), as well as the α2A adrenoreceptor (α2A AR), were detected in the tenocytes, both in vivo in the rabbit tissue and in vitro in the human tendon cells. As a response to mechanical loading in the in vivo model, the intratendinous levels of SP increased, and this elevation was found to precede distinct tendinosis changes. The in vitro model demonstrated the same response to load, i.e. an increased SP expression, but in this case also a decrease in the NK-1 R expression. In the in vivo model, exogenously administered SP, as well as clonidine (an α2 AR agonist), accelerated tenocyte hypercellularity, an effect that was not seen when administrating a specific α2A AR antagonist. Exogenous administration of SP also resulted in intratendinous angiogenesis and paratendinous inflammation. In the in vitro model, both SP and clonidine had proliferative effects on the human tenocytes, specifically mediated via NK-1R and α2A AR, respectively; both of which in turn involved activation/phosphorylation of the extracellular signal-regulated kinases 1 and 2 (ERK1/2). Exogenously administered SP, in Anti-Fas induced apoptosis of the tenocytes in vitro, confirmed SP to have an anti-apoptotic effect on these cells. This effect was specifically mediated via NK-1 R and the known anti-apoptotic Akt pathway. Conclusions: In summary, this thesis concludes that stimulation of NK-1 R and α2A AR on tenocytes, both in vitro and in vivo, mediates significant cell signalling effects leading to processes known to occur in tendinosis, including hypercellularity. The pathological role of the hypercellularity in tendinosis is still unclear, but it is likely to affect collagen metabolism/turnover and arrangement, and thereby indirectly tendon biomechanical function. Additional evidence is here provided showing that SP not only causes tenocyte proliferation, but also contributes to anti-apoptotic events. Furthermore, it was concluded that SP may be involved in the development of tendinosis, since its production is increased in response to load, preceding tendinosis, and since SP accelerates tendinosis changes, through some mechanistic pathways here delineated. These findings suggest that inhibition of SP, and possibly also catecholamines, could be beneficial in the reconstitution/normalization of tendon structure in tendinosis.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Tenocytes are the principal cells of the human Achilles tendon. In tendinosis, changes in the metabolism and morphology of these cells occur. Neurotrophins are growth factors essential for the development of the nervous system. Tumour necrosis factor alpha (TNF-α) has been found to kill sarcomas but has destructive effects in several major diseases. The two systems have interaction effects and are associated with apoptosis, proliferation, and pain signalling in various diseases. Whether these systems are present in the Achilles tendon and in Achilles tendinosis is unknown. The hypothesis is that the tenocytes produce substances belonging to these systems. In Studies I–III, we show that the potent effects of these substances are also likely to occur in the Achilles tendon. We found tenocyte immunoreactions for the neurotrophins brain-derived neurotrophic factor (BDNF), the nerve growth factor (NGF), the neurotrophin receptor p75, and for TNF-α and both of its receptors, TNFR1 and TNFR2. This occurred in both subjects with painful mid-portion Achilles tendinosis, and in controls. Furthermore, we found mRNA expression for BDNF and TNF-α in tenocytes, which proves that these cells produce these substances. TNFR1 mRNA was also detected for the tenocytes, and TNFR1 immunoreactions were upregulated in tendinosis tendons. This might explain why tenocytes in tendinosis undergo apoptosis more often than in normal tendons. Total physical activity (TPA) level and blood concentration of both soluble TNFR1 and BDNF were measured in Study IV. The results showed that the blood concentration of both factors were similar in subjects with tendinosis and in controls. Nevertheless, the TPA level was related to the blood concentration of sTNFR1 in tendinosis, but not in controls. This relationship should be studied further. The findings of this doctoral thesis show that neurotrophin and TNF-α systems are expressed in the Achilles tendon. We believe that the functions include tissue remodelling, proliferation and apoptosis.

Sammanfattning Syfte och frågeställningar: Syftet med studien var att utvärdera förändringar över tid vid excentrisk träning av quadriceps i en ny dosering i kombination med träning av höft- och bålmuskulatur under 12 veckor vid patellar tendinopti med avseende på a) smärta, b) skattning av symtom, funktion och förmåga att delta i idrott, c) funktionellt hopptest samt c) vävnadsförändringar i patellarsenan. Metod: Studien var en pilotstudie utan kontrollgrupp. Tolv personer som kliniskt diagnostiserats med patellar tendinopati samt hade ultraljudsverifierad tendinos i patellarsenan deltog frivilligt i studien (2 kvinnor och 10 män; medelålder 29,2 år, besvärsduration &gt; tre månader). För att utvärdera träningsinterventionen användes visuell analog skala (VAS) för smärta i vila och under aktivitet, frågeformuläret Victorian Institute of Sport Assessment score (VISA-P) för skattning av symtom, funktion och förmåga att delta i idrott, funktionellt hopptest, one-leg hop for distance (OLH). Undersökning av patellarsenan gjordes med ultraljud och färgdoppler. Utvärdering genomfördes före och efter tolv veckors träningsintervention. Träningsprogrammet innehöll excentrisk träning av quadriceps (bromsande knäböjning på ett ben) stående på en kil inklusive stretch av quadriceps i kombination med träning av höft- och bålmuskulaturen som utfördes tre gånger i veckan under 12 veckor. Signifikansnivå p &lt; 0.05 användes i studien och en tendens inkluderades mellan 0.05 &lt; p &lt; 0.1 Resultat: Efter träningsperioden sågs en signifikant minskning av smärta i vila (VAS från 64 till 11,5) och under aktivitet (från 80 till 21 på VAS skalan) samt en ökad funktion och förmåga att delta i idrott sågs på VISA-P (från 44 till 71,5). En signifikant förbättrings sågs också på funktionellt hopptest på ett ben med en ökad hopplängd (från 103 till 132 cm) efter träningsinterventionen. Ingen signifikant skillnad kunde ses gällande vävnadsförändringar i patellarsenan. Det fanns däremot en tendens (p=.083) till förbättring av senstrukturen i patellarsenan efter träningsinterventionen. Slutsats: Efter tolv veckors intervention sågs en signifikant förbättring med avseende på smärta och funktion vid patellar tendinopati. Dessa resultat bör följas upp för att utvärdera långsiktiga förändringar av träningsinterventionen. Resultaten från denna pilotstudie kan ligga till grund för en kommande randomiserad kontrollerad interventionsstudie. / Abstract Aim: The aim of this study was to evaluate changes over time during eccentric quadriceps training with a previously unstudied exercise dosage in combination with hip and core exercises for a period of 12 weeks in patients with patellar tendinopathy. The outcome measures were: pain, self-evaluated symptoms, functions and ability to participate in sport, functional jumptest and patellar tendon tissue changes. Method: This was an uncontrolled pilot study. Twelve patients diagnosed with patellar tendinopathy using clinical testing and ultrasound imaging participated in the study voluntarily (2 female and 10 men, mean age 29.2 years, duration of symptoms &gt; 3 months). To evaluate the intervention a visual analogue scale (VAS) was used to measure pain at rest and during activity. The Victorian Institute of Sport Assessment score (VISA-P) was used to evaluate self-assessed symptoms, function and ability to participate in sport. One-leg hop test for distance (OLH) was used as a functional test. Changes in the patellar tendon were examined using ultrasound imaging and colour doppler. Measurements took place at baseline and at 12 weeks. The exercise program contained eccentric quadriceps training (drop-squat on one leg) standing on a decline board, quadriceps stretching in combination with hip and core exercises performed 3 times per week for twelve weeks. P-value was set at &lt; 0.05 and a tendency was included between 0.05 &lt; p &lt; 0.1 Results: At 12 weeks a significant reduction of pain was observed at rest (from 64 to 11.5) and during activity (from 80 to 21) as well as improved VISA-P scores (from 44 to 71.5). A significant improvement was observed on the functional hop test (from 103 to 132 cm). No significant changes in the patellar tendon were observed with ultrasound imaging. Although there was a tendency towards structural improvement of the patellar tendon (p=.083) after 12 weeks of intervention. Conclusion: After twelve weeks of intervention a significant improvement was observed with respect to pain and function. It would be of interest to examine long-term changes of this combined training program. These results may be used as a foundation for a future randomised controlled intervention study.