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Presence of the neuropeptide Y 1 receptor in tenocytes and blood vessel walls in the human Achilles tendon
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
2009 (English)In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 13, 1136-1142 p.Article in journal (Refereed) Published
Abstract [en]

Background: There are still questions concerning the mechanisms of development of chronic pain and impaired function of tendons (tendinosis). Aspects that are known to occur are cell proliferation, angiogenesis and altered blood flow regulation. Neuropeptide NPY (NPY) is widely distributed in the body and has powerful effects in relation to these processes. NPY has its effects via the G-protein-coupled Y receptors. There is no information concerning the presence or absence of NPY receptors in Achilles tendons or other tendons.

Objective: To clarify the expression patterns of the NPY receptors Y1 and Y2 in normal and tendinosis Achilles tendons of man.

Methods: Immunohistochemical methods were used. Examination on NPY was carried out in parallel.

Results: The tenocytes showed strong immunoreactions for the Y1 receptor. The immunoreactions were more intense in the tenocytes of the tendinosis tendons than in those of the non-tendinosis tendons. The rounded/oval tenocytes typically seen in tendinosis tendons exhibited marked Y1 receptor reactions on their exterior. Pronounced Y1 reactions were seen in the smooth muscle of the arterioles of both tendinosis and non-tendinosis tendons. No reactions for the Y2 receptor were noted. NPY was detected in nerve fascicles and in the perivascular innervation.

Conclusions: The present study shows that there is a morphologic correlate for the occurrence of pronounced NPY effects via the Y1 receptor in both tenocytes, this especially being a fact for tendinosis tendons, and blood vessel walls in the Achilles tendon. The findings are of particular interest as NPY is known to have proliferative, angiogenic and blood vessel regulating effects. The effects of targeting the Y1 receptor in tendinosis is an interesting task to be further evaluated.

Place, publisher, year, edition, pages
BMJ Publishing Group , 2009. Vol. 43, no 13, 1136-1142 p.
National Category
Medical and Health Sciences
Research subject
Human Anatomy
Identifiers
URN: urn:nbn:se:umu:diva-30282DOI: 10.1136/bjsm.2008.055780OAI: oai:DiVA.org:umu-30282DiVA: diva2:281376
Available from: 2009-12-15 Created: 2009-12-15 Last updated: 2012-10-10Bibliographically approved
In thesis
1. The human Achilles tendon: innervation and intratendinous production of nerve signal substances - of importance in understanding the processes of Achilles tendinosis
Open this publication in new window or tab >>The human Achilles tendon: innervation and intratendinous production of nerve signal substances - of importance in understanding the processes of Achilles tendinosis
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2010. 88 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1321
Keyword
Achilles tendon, tendinosis, tendinopathy, nerve signal substances, hälsena, Achillessena, tendinos, tendinopati
National Category
Surgery
Research subject
Human Anatomy
Identifiers
urn:nbn:se:umu:diva-30284 (URN)978-91-7264-929-3 (ISBN)
Public defence
2010-01-15, Biologihuset, sal BiA201, Umeå universitet, Umeå, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2009-12-23 Created: 2009-12-15 Last updated: 2009-12-23Bibliographically approved

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Alfredson, HåkanForsgren, Sture

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