| 1. |
- Andersson, Gustav, 1983-, et al.
(författare)
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Nerve-related characteristics of ventral paratendinous tissue in chronic Achilles tendinosis
- 2007
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - 0942-2056. ; 15:10, s. 1272-1279
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Andersson, Gustav, 1983-, et al.
(författare)
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Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon
- 2008
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Ingår i: Regulatory Peptides. - 0167-0115. ; 150:1-3, s. 81-87
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Tidskriftsartikel (refereegranskat)abstract
- Nerve signal substances, such as the tachykinin substance P (SP), may be involved in the changes that occur in response to tendinopathy (tendinosis). It is previously known that the level of SP innervation within tendon tissue is limited, but results of experimental studies have suggested that SP may have stimulatory, angiogenetic and healing effects in injured tendons. Therefore, it would be of interest to know if there is a local SP-supply in tendon tissue. In the present study, the patterns of expression of SP and its preferred receptor, the neurokinin-1 receptor (NK-1 R), in normal and tendinosis human Achilles tendons were analyzed by use of both immunohistochemistry and in situ hybridization. We found that there was expression of SP mRNA in tenocytes, and that tenocytes showed expression of NK-1 R at protein as well as mRNA levels. The observations concerning both SP and NK-1 R were most evident for tenocytes in tendinosis tendons. Our findings suggest that SP is produced in tendinosis tendons, and furthermore that SP has marked effects on the tenocytes via the NK-1 R. It cannot be excluded that the SP effects are of importance concerning the processes of reorganization and healing that occur for tendon tissue in tendinosis. In conclusion, it appears as if SPergic autocrine/paracrine effects occur in tendon tissue during the processes of tendinosis, hitherto unknown effects for human tendons.
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| 3. |
- Andersson, Gustav, 1983-, et al.
(författare)
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Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy : contralateral effects suggest the involvement of central neuronal mechanisms
- 2011
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Ingår i: British Journal of Sports Medicine. - 0306-3674. ; 45:5, s. 399-406
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Tidskriftsartikel (refereegranskat)abstract
- Objective To determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons. Design Four groups of six New Zealand white rabbits per group were used. The animals of one (control) group were not subjected to exercise/stimulation. Interventions Animals were subjected to a protocol of electrical stimulation and passive flexion-extension of the right triceps surae muscle every second day for 1, 3 or 6 weeks. Main Outcome Measures Tenocyte number and vascular density were calculated. Morphological evaluations were also performed as well as in-situ hybridisation for vascular endothelial growth factor (VEGF) messenger RNA. Results There was a significant increase in the tenocyte number after 3 and 6 weeks of exercise, but not after 1 week, in comparison with the control group. This was seen in the Achilles tendons of both legs in experimental animals, including the unexercised limb. The pattern of vascularity showed an increase in the number of tendon blood vessels in rabbits that had exercised for 3 weeks or more, compared with those who had exercised for 1 week or not at all. VEGF-mRNA was detected in the investigated tissue, with the reactions being more clearly detected in the tendon tissue with tendinosis-like changes (6-week rabbits) than in the normal tendon tissue (control rabbits). Conclusions There were bilateral tendinosis-like changes in the Achilles tendons of rabbits in the current model after 3 weeks of training, suggesting that central neuronal mechanisms may be involved and that the contralateral side is not appropriate as a control.
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| 4. |
- Bagge, Johan, et al.
(författare)
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Physical activity level in Achilles tendinosis is associated with blood levels of pain-related factors : a pilot study
- 2011
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - 0905-7188. ; 21:6, s. E430-E438
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity affects the pain symptoms for Achilles tendinosis patients. Brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha) and their receptors have been detected in human Achilles tendon. This pilot study aimed to compare serum BDNF and soluble tumor necrosis factor receptor I (sTNFRI) levels in Achilles tendinosis patients and healthy controls and to examine the influence of physical activity, and BMI and gender, on these levels. Physical activity was measured with a validated questionnaire, total physical activity being the parameter analyzed. Physical activity was strongly correlated with BDNF among tendinosis women [Spearman's rho (rho) = 0.90, P < 0.01] but not among control women (rho = -0.08, P = 0.83), or among tendinosis and control men. Physical activity was significantly correlated with sTNFRI in the entire tendinosis group and among tendinosis men (rho = 0.65, P = 0.01), but not in the entire control group or among control men (rho = 0.04, P = 0.91). Thus, the physical activity pattern is related to the TNF and BDNF systems for tendinosis patients but not controls, the relationship being gender dependent. This is new information concerning the relationship between physical activity and Achilles tendinosis, which may be related to pain for the patients. This aspect should be further evaluated using larger patient materials.
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| 5. |
- Bjur, Dennis, 1965-, et al.
(författare)
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Immunohistochemical and in situ hybridization observations favor a local catecholamine production in the human Achilles tendon
- 2008
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Ingår i: Histology and Histopathology. - 0213-3911. ; 23:2, s. 197-208
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Tidskriftsartikel (refereegranskat)abstract
- Results of recent studies using immunohistochemistry show evidence of an occurrence of catecholamine production in the cells (tenocytes) of patellar tendons exhibiting tendinopathy (tendinosis). In the present study, antibodies against the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) and alpha1-adrenoreceptors were applied to sections of specimens of normal and tendinosis Achilles tendons. In situ hybridization using a probe detecting human TH mRNA was also utilized. It was found that sympathetic innervation was very scarce. On the other hand, there were distinct alpha1-adrenoreceptor immunoreactions in blood vessel walls. Interestingly, tenocytes, particularly from tendinosis samples in which the tenocytes showed an abnormal shape (not the typical slender appearance), displayed TH immunoreactions and reactions for TH mRNA. Of further interest was the finding of alpha1-adrenoreceptor immunoreactions in tenocytes. The observations show not only evidence of local catecholamine production at the protein level, which was the case in recent studies for the patellar tendon, but also at the mRNA level. The observations suggest that the tenocytes, especially those with disfigured appearances in tendinosis, can produce catecholamines and also that they can respond to sympathetic transmitters. This is of interest as adrenergic stimulation in other parts of the body is known to induce degenerative/apoptotic and proliferative events, features which are seen in Achilles tendinosis. These observations are completely new findings concerning the human Achilles tendon. It is likely that locally produced catecholamines and the occurrence of autocrine/paracrine effects of these substances are of great relevance during the process of tendinosis.
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| 6. |
- Bjur, Dennis, 1965-, et al.
(författare)
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Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors : new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)
- 2008
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Ingår i: Cell and Tissue Research. - 0302-766X. ; 331:2, s. 385-400
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Tidskriftsartikel (refereegranskat)abstract
- Limited information is available concerning the existence of a cholinergic system in the human Achilles tendon. We have studied pain-free normal Achilles tendons and chronically painful Achilles tendinosis tendons with regard to immunohistochemical expression patterns of the M(2) muscarinic acetylcholine receptor (M(2)R), choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). M(2)R immunoreactivity was detected in the walls of blood vessels. As evidenced via parallel staining for CD31 and alpha-smooth muscle actin, most M(2)R immunoreactivity was present in the endothelium. M(2)R immunoreactivity also occured in tenocytes, which regularly immunoreact for vimentin. The degree of M(2)R immunoreactivity was highly variable, tendinosis tendons that exhibit hypercellularity and hypervascularity showing the highest levels of immunostaining. Immunoreaction for ChAT and VAChT was detected in tenocytes in tendinosis specimens, particularly in aberrant cells. In situ hybridization revealed that mRNA for ChAT is present in tenocytes in tendinosis specimens. Our results suggest that autocrine/paracrine effects occur concerning the tenocytes in tendinosis. Up-regulation/down-regulation in the levels of M(2)R immunoreactivity possibly take place in tenocytes and blood vessel cells during the various stages of tendinosis. The presumed local production of acetylcholine (ACh), as evidenced by immunoreactivity for ChAT and VAChT and the detection of ChAT mRNA, appears to evolve in response to tendinosis. These observations are of importance because of the well-known vasoactive, trophic, and pain-modulating effects that ACh is known to have and do unexpectedly establish the presence of a non-neuronal cholinergic system in the Achilles tendon.
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| 7. |
- Danielson, Patrik, et al.
(författare)
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Distribution of general (PGP 9.5) and sensory (substance P/CGRP) innervations in the human patellar tendon.
- 2006
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - 0942-2056. ; 14:2, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- There is no information on the pattern of blood vessel innervation, and in principle no information on innervation in general, in the human patellar tendon. In the present study, biopsies from the proximal part of normal and pain-free patellar tendons (11 men, mean age 33 years) were examined. The specimens were evaluated by using antibodies against the general nerve marker protein gene-product 9.5 (PGP 9.5) and the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and immunohistochemistry. It was observed that the arteries, and to some extent the small vessels, in the loose paratendinous connective tissue were supplied with PGP 9.5- as well as SP- and CGRP-innervations. There was a marked PGP 9.5-like immunoreaction (LI), and to some extent also SP- and CGRP-LI, in the large nerve fascicles in this tissue. In the tendon tissue proper, PGP 9.5-LI was detected in nerve fibers located in the vicinity of some of the blood vessels and in thin nerve fascicles. There was a low degree of SP- and CGRP-innervation in the tendon tissue proper. The observations give a morphologic correlate for the occurrence of nerve-mediated effects in the patellar tendon. Particularly it seems as if there is a marked nerve-mediated regulation of the blood vessels supplying the tendon, at the level where they course in the loose paratendinous connective tissue.
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| 8. |
- Danielson, Patrik, et al.
(författare)
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Extensive expression of markers for acetylcholine synthesis and of M2 receptors in tenocytes in therapy-resistant chronic painful patellar tendon tendinosis - a pilot study.
- 2007
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Ingår i: Life Sciences. - 0024-3205. ; 80:24-25, s. 2235-2238
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Tidskriftsartikel (refereegranskat)abstract
- We have recently obtained evidence favoring the occurrence of an up-regulation of a non-neuronal cholinergic system in chronic painful patellar tendon tendinosis. It seems possible that this up-regulation to a certain degree may be involved in the manifestations of the disease. Today, there is a new, very successful, line of treatment of patellar tendinosis in the form of Doppler guided sclerosing injections. However, a few patients seem resistant to this therapy. Therefore, we have in this pilot study investigated biopsies from the patellar tendon of three such therapy-resistant patients, using immunohistochemistry. In situ hybridization was also applied. Comparisons were made with a material of specimens from both normal (n=16) and tendinosis (n=7) tendons, also previously examined. The study showed that there were extensive immunoreactions for choline acetyltransferase (ChAT) and vesicular acetylcholine transporter, as well as for the M(2) muscarinic acetylcholine receptor, in the overwhelming majority of the tenocytes. The immunoreactions were more pronounced than those generally obtained in the tendinosis tissue of the previously studied patients and clearly more pronounced than those of patellar tendon tissue of controls. Also, for the first time, we here present findings of mRNA for ChAT within tenocytes. In conclusion, it appears as if there is an excessive local acetylcholine (ACh) production and an occurrence of marked ACh effects in cases of severe tendinosis. An excessive production of local ACh might be related to pain sensation and the processes that occur in tendinosis development, such as cell proliferation. Thus, the results of this pilot study suggest that non-neuronal ACh is highly involved in the pathology of therapy-resistant patellar tendinosis.
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| 9. |
- Danielson, Patrik, et al.
(författare)
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Immunohistochemical and histochemical findings favoring the occurrence of autocrine/paracrine as well as nerve-related cholinergic effects in chronic painful patellar tendon tendinosis.
- 2006
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Ingår i: Microscopy research and technique (Print). - 1059-910X. ; 69:10, s. 808-819
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Tidskriftsartikel (refereegranskat)abstract
- The pathogenesis of the pain in patellar tendon tendinosis ("jumper's knee") is unclear. We have recently presented new information about the sensory nervous system in the human patellar tendon, but there is very little information regarding the possible occurrence of a cholinergic system in this tendon. In the present study, specimens of pain-free normal tendons and chronically painful tendinosis tendons were examined by different immunohistochemical and histochemical methods. Antibodies against the M(2) receptor, choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT) were applied, and staining for demonstration of activity of acetylcholinesterase (AChE) was also utilized. It was found that immunoreactions for the M(2) receptor could be detected intracellularly in both blood vessel cells and tenocytes, especially in tendinosis specimens. Furthermore, in the tendinosis specimens, some tenocytes were seen to exhibit immunoreaction for ChAT and VAChT. AChE reactions were seen in fine nerve fibers associated with small blood vessels in both the normal control tendons and the tendinosis tendons. The observations suggest that there is both a nerve related and a local cholinergic system in the human patellar tendon. As ChAT and VAChT immunoreactions were detected in tenocytes of tendinosis tendons, these cells might be a source of local acetylcholine (Ach) production. As both tenocytes and blood vessel cells were found to exhibit immunoreactions for the M(2) receptor, it is likely that both of these tissue cells may be influenced by ACh. Thus, in conclusion, there appears to be an upregulation of the cholinergic system, and an occurrence of autocrine/paracrine effects in this system, in the tendinosis patellar tendon.
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| 10. |
- Danielson, Patrik, et al.
(författare)
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In situ hybridization studies confirming recent findings of the existence of a local nonneuronal catecholamine production in human patellar tendinosis.
- 2007
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Ingår i: Microscopy research and technique (Print). - 1059-910X. ; 70:10, s. 908-911
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Tidskriftsartikel (övrigt vetenskapligt)abstract
- We have in recent studies presented unexpected immunohistochemical evidence favoring the existence of a local production of catecholamines, and an occurrence of adrenergic receptors on the tendon cells (tenocytes), in the human patellar tendon. This was particularly noticed for tendons from patients suffering from tendinosis (chronic tendon pain), which has led us to propose an involvement of this autocrine/paracrine system in the development of tendinosis, especially since catecholamines have been reported to be modulators of tissue remodeling and pain processes. However, the findings concerning catecholamine production have so far only been noted at the level of protein detection, and for this reason, the aim of the present study was to confirm the previous immunohistochemical results by using in situ hybridization (ISH) technique. A ssDNA probe detecting human mRNA for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) was applied. The ISH results revealed that there were clear reactions indicating the existence of mRNA for TH in tenocytes of tendinosis specimens. It was generally noted that disfigured tenocytes were the ones with the most distinct reactions, while normally looking tenocytes hardly displayed any reactions at all. In conclusion, this study presents the first evidence at the mRNA level of the existence of a local nonneuronal production of catecholamines in human patellar tendon tissue. The findings add to recent observations of the occurrence of a local production in tendons of signal substances traditionally related to neurons.(c) 2007 Wiley-Liss, Inc.
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