Studies on the importance of sympathetic innervation, adrenergic receptors, and a possible local catecholamine production in the development of patellar tendinopathy (tendinosis) in man

Abstract

Changes in the patterns of production and in the effects of signal substances may be involved in the development of tendinosis, a chronic condition of pain in human tendons. There is no previous information concerning the patterns of sympathetic innervation in the human patellar tendon. In this study, biopsies of normal and tendinosis patellar tendons were investigated with immunohistochemical methods, including the use of antibodies against tyrosine hydroxylase (TH) and neuropeptide Y, and against alpha1-, alpha2A-, and beta1-adrenoreceptors. It was noticed that most of the sympathetic innervation was detected in the walls of the blood vessels entering the tendon through the paratendinous tissue, and that the tendon tissue proper of the normal and tendinosis tendons was very scarcely innervated. Immunoreactions for adrenergic receptors were noticed in nerve fascicles containing both sensory and sympathetic nerve fibers. High levels of these receptors were also detected in the blood vessel walls; alpha1-adrenoreceptor immunoreactions being clearly more pronounced in the tendinosis tendons than in the tendons of controls. Interestingly, immunoreactions for adrenergic receptors and TH were noted for the tendon cells (tenocytes), especially in tendinosis tendons. The findings give a morphological correlate for the occurrence of sympathetically mediated effects in the patellar tendon and autocrine/paracrine catecholamine mechanisms for the tenocytes, particularly, in tendinosis. The observation of adrenergic receptors on tenocytes is interesting, as stimulation of these receptors can lead to cell proliferation, degeneration, and apoptosis, events which are all known to occur in tendinosis. Furthermore, the results imply that a possible source of catecholamine production might be the tenocytes themselves

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].…”

Neuropeptides in tendinopathy

“…Tendons are sparsely innervated, as the majority of sensory and autonomic nerves run in close proximity to the vascular supply in the paratendon and endotendon (11,18,20). Extensive studies of patellar, Achilles and extensor carpi radialis brevis tendon innervation have recently been conducted (11,18,20).…”

“…Extensive studies of patellar, Achilles and extensor carpi radialis brevis tendon innervation have recently been conducted (11,18,20). In all the tendons examined, a general nerve marker (protein gene product /PGP 9.5) has demonstrated that the paratendinous tissue is well supplied with nerve fibres and fascicles.…”

“…Whether the initiating event is due to collagen fibril and microvessel failure, or rather to load-induced responses in tenocytes, remains a subject of debate (6,7). However, the chronic pathological changes in the tendon and paratendon can be substantial and include an aberrant increase of microvessels and sensory nerves, abnormal quality and accelerated remodeling of the extracellular matrix, and increased local metabolism with excessive lactate production (8)(9)(10)(11)(12).…”

“…In particular, tendon vasculature is associated with autonomic nerves that may regulate blood flow, as well as sensory nerves that are strongly implicated as a source of tendon pain (11,18,19).…”