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.

Neuropeptides in tendinopathy

“…To a lesser extent, PGP 9.5 is also present in nerve fibres and fascicles within the tendon proper itself, i.e. not associated with vessels (11,20,22).…”

“…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.…”

“…The human tendon nerve supply demonstrates sympathetic markers including tyrosine hydroxylase and neuropeptide Y (11). Acetylcholine esterase reactions have also been identified in fine nerve fibers associated with small blood vessels in the patellar and Achilles tendons, demonstrating the existence of a parasympathetic innervation (20). Acetylcholine is well known as a vasodilator, while sympathetic neuropeptides mediate vasoconstriction.…”

“…Acetylcholine is well known as a vasodilator, while sympathetic neuropeptides mediate vasoconstriction. Indeed, tendon blood vessels express receptors both for sympathetic (alpha-adrenergic) as well as for parasympathetic (M2 muscarinic) neuropeptide receptors (11,20). Vasoactive intestinal peptide (a vasodilatory parasympathetic neuropeptide) has also been demonstrated in rat tendons via immunohistochemistry and radioimmunoassay (25).…”