The Cholinergic System Can Be of Unexpected Importance in Osteoarthritis

The main belief is that joints such as the knee and ankle joints are not innervated by nerves with a cholinergic function. That includes the assumption that these joints are not innervated by the vagus nerve (van Maanen et al., 2009a, see also Grimsholm et al., 2008). Accordingly, there is actually no morphologic proof of a cholinergic innervation of the knee joint, nor of the ankle joint. Despite this fact, it is shown that electrical and pharmacological stimulation of the vagus nerve has a diminishing effect on carragenan-induced paw inflammation in rats (Borovikova et al., 2000a) and that interference with the effects of the vagus nerve leads to effects on the knee joint arthritis as seen experimentally (van Maanen et al., 2009b). There are also other findings which show the potential effects that interference with vagal effects has on joint inflammation. These will be discussed below. It is actually strange that interference with cholinergic effects, as via manpulations of the vagus nerve, has effects in knee joint inflamed synovium without presence of a vagal nerve innervation. One possibility is that the effects are indirect, via an occurrence of vagal effects on other sites such as the spleen (Huston et al., 2006, see also van Maanen et al., 2009a). However, another possibility is that there is a non-neuronal production of acetylcholine (ACh) within the synovial tissue itself. This has actually been shown to be the case (Grimsholm et al., 2008) (see further in paragraph 3).