Novel information on the non-neuronal cholinergic system in orthopedics provides new possible treatment strategies for inflammatory and degenerative diseases

Abstract

Anti-cholinergic agents are used in the treatment of several pathological conditions. Therapy regimens aimed at up-regulating cholinergic functions, such as treatment with acetylcholinesterase inhibitors, are also currently prescribed. It is now known that not only is there a neuronal cholinergic system but also a non-neuronal cholinergic system in various parts of the body. Therefore, interference with the effects of acetylcholine (ACh) brought about by the local production and release of ACh should also be considered. Locally produced ACh may have proliferative, angiogenic, wound-healing, and immunomodulatory functions. Interestingly, cholinergic stimulation may lead to anti-inflammatory effects. Within this review, new findings for the locomotor system of a more widespread non-neuronal cholinergic system than previously expected will be discussed in relation to possible new treatment strategies. The conditions discussed are painful and degenerative tendon disease (tendinopathy/tendinosis), rheumatoid arthritis, and osteoarthritis.

Keywords: acetylcholine; osteoarthritis.; rheumatoid arthritis; tendinopathy; tendinosis.

Figure 1

Schematic drawing of human tendon tissue showing the occurrence of a non-neuronal cholinergic system in tendinosis. Violet dots represent acetylcholine (ACh) that is locally produced in tenocytes of pathological appearance (unfilled arrow). Normal looking tenocytes (filled arrow) do not produce ACh. ^– ACh can influence 1) nerves, 2) cells of blood vessel walls, and 3) the tenocytes themselves. These structures have been shown to be supplied with muscarinic ACh receptors of subtype M₂ (M2R).^– Image by Gustav Andersson.