Immunohistochemical and histochemical findings favoring the occurrence of autocrine/paracrine as well as nerve-related cholinergic effects in chronic painful patellar tendon tendinosis.
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.
Article: A randomized controlled trial of exercise versus wait-list in chronic tennis elbow (lateral epicondylosis).[show abstract] [hide abstract]
ABSTRACT: Chronic tennis elbow (lateral epicondylosis) is a common disorder. Like other chronic soft-tissue pain conditions it is often difficult to treat successfully. The effects of exercise have been discussed, but no convincing evidence has been put forward so far, and a simple protocol for exercise is lacking. This study is a randomized, controlled, clinical trial of the effect of exercise versus expectation (wait-list) on pain, muscle strength, function, and quality of life in patients with long-standing lateral epicondylosis. Eighty-one subjects with tennis elbow lasting for more than 3 months were randomly allocated to an exercise group (n = 40) or a reference group (n = 41). The exercise group performed daily exercise, with weekly load increase, for 3 months. The reference group was wait-listed, but otherwise followed in the same way. Outcome measures were pain during maximum voluntary muscle contraction (Cozen's test) and pain during maximum muscle elongation with a load (modified Empty-can-test); muscle strength was measured with a Chatillon MSE 100 hand-held dynamometer, and the Disability of the Arm, Shoulder and Hand (DASH) and the Gothenburg Quality of Life questionnaires. The exercise group had greater and faster regression of pain, both during muscle contraction and muscle elongation, than the reference group (p = 0.0005 and p = 0.0016, respectively). There was a non-significant muscle strength difference between the groups, but no differences regarding DASH scores or quality of life measures. Exercise appears to be superior to expectation in reducing pain in chronic lateral epicondylosis.Upsala journal of medical sciences 11/2011; 116(4):269-79. · 0.73 Impact Factor
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ABSTRACT: It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell© technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10⁻⁷ M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.PLoS ONE 01/2011; 6(11):e27209. · 4.09 Impact Factor