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Nerve-related characteristics of ventral paratendinous tissue in chronic Achilles tendinosis
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
2007 (English)In: Knee Surgery, Sports Traumatology, Arthroscopy, ISSN 0942-2056, E-ISSN 1433-7347, Vol. 15, no 10, 1272-1279 p.Article in journal (Refereed) Published
Abstract [en]

Ultrasound and Doppler examination has shown high blood flow-neovascularisation inside and outside the ventral Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. In patients with Achilles tendinosis, injections with the sclerosing substance polidocanol, targeting the areas with increased blood flow, have been demonstrated to give pain relief. A drawback when interpreting these findings is the fact that the pattern of nerve supply in the target area, i.e. the ventral area of the tendon, is so far unknown. In this study, therefore, tissue specimens from this area, obtained during surgical treatment of patients with chronic painful midportion Achilles tendinosis, were examined. In the examined area, containing loose connective tissue, the general finding was a presence of large and small arteries and nerve fascicles. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5. The nerve fascicles contain sensory nerve fibers, as shown via staining for the sensory markers substance P (SP) and calcitonin gene-related peptide, and sympathetic nerve fibers as seen via processing for tyrosine hydroxylase. In addition, there were immunoreactions for the SP-preferred receptor, the neurokinin-1 receptor, in blood vessel walls and nerve fascicles. Some of the blood vessels were supplied by an extensive peri-vascular innervation, sympathetic nerve fibers being a distinct component of this innervation. There was also a marked occurrence of immunoreactions for the alpha1-adrenoreceptor in arterial walls as well as in the nerve fascicles. Altogether, these findings suggest that the area investigated is under marked influence by the nervous system, including sympathetic and sensory components. Thus, sympathetic/sensory influences may be involved in the pain mechanisms from this area. In conclusion, the nerve-related characteristics of the area targeted by the polidicanol injection treatment for Achilles tendinosis, are shown here for the first time.

Place, publisher, year, edition, pages
2007. Vol. 15, no 10, 1272-1279 p.
Keyword [en]
Achilles tendon, Tendinosis, Sympathetic innervation, Sensory innervation
National Category
Cell and Molecular Biology
Research subject
Human Anatomy
Identifiers
URN: urn:nbn:se:umu:diva-8147DOI: 10.1007/s00167-007-0364-2PubMedID: 17604979OAI: oai:DiVA.org:umu-8147DiVA: diva2:147818
Available from: 2008-01-15 Created: 2008-01-15 Last updated: 2017-12-14Bibliographically approved
In thesis
1. Influences of paratendinous innervation and non-neuronal substance P in tendinopathy: studies on human tendon tissue and an experimental model of Achilles tendinopathy
Open this publication in new window or tab >>Influences of paratendinous innervation and non-neuronal substance P in tendinopathy: studies on human tendon tissue and an experimental model of Achilles tendinopathy
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2010. 104 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1370
Keyword
Achilles tendon, tendinopathy, tendinosis, paratenon, innervation, substance P, neuropeptides, neurokinin-1 receptor
National Category
Cell and Molecular Biology
Research subject
Human Anatomy
Identifiers
urn:nbn:se:umu:diva-35917 (URN)978-91-7459-067-8 (ISBN)
Public defence
2010-10-01, Betula, Byggnad 6M, NUS, Umeå University, SE-901 87 Umeå, Sweden, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2010-09-13 Created: 2010-09-09 Last updated: 2010-09-13Bibliographically approved

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