In situ hybridization studies confirming recent findings of the existence of a local nonneuronal catecholamine production in human patellar tendinosis

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.

The Basic Science of Tendinopathy

“…The presence of neovascularization and innervation, and the increase of neurotransmitter in tendinopathy may be part of the reason tendinopathy patients often have chronic pain [1,3,82]. Danielson et al [32,33] recently reported the tenocytes in tendinosis patellar tendon exhibited more immunoreactions for adrenergic receptors and catecholamine. These findings are of relevance as studies have demonstrated stimulation of adrenergic receptors can lead to cell proliferation and/or cell degeneration and apoptosis [6,23].…”

Ultrasound-Guided EPI® Technique and Eccentric Exercise, New Treatment for Achilles and Patellar Tendinopathy Focused on the Region-Specific of the Tendon

“…This growth of nerve fibers, which causes chronic pain, could be part of a process of abnormal tissue repair, preceded by repetitive microtrauma [53].…”

Neuropeptides in tendinopathy

“…Immunohistochemistry and in situ hybridization have both shown that tyrosine hydroxylase is expressed by tenocytes within the human patellar tendon (11,45,46). Additionally, these same tenocytes demonstrate immunoreactions for alpha-adrenergic receptors (11).…”

“…Adrenaline / Noradrenaline (TH 1 ) Sympathetic nerves; tenocytes (11,29,45) Acetylcholine (AchE 2 , ChAT 3 )…”

“…Nerves; blood vessels; tenocytes (22,55,62) M 2 R 2 (Acetylcholine receptor) Blood vessels; tenocytes (20) Alpha-adrenergic (Catecholamine receptor) Sympathetic nerves; blood vessels; tenocytes (11,45) NMDAR-1 3 (Glutamate receptor) Sensory nerves; tenocytes (53,63) …”