20. The peripheral nervous system and focal bony erosions in arthritis

Sympathetic and sensory nerve fibers innervate bone and joint adjacent tissue. Apart from transmitting signals to the brain they also play an important role in bone homeostasis. Under certain conditions (see sweat glands) sympathetic nerve fibers can change their phenotype from noradrenergic to cholinergic. Anti-inflammatory effects mediated by the alpha-7 subunit-containing nicotinic acetylcholine receptor have been described. We asked whether this transition could also occur near focal erosions during collagen-induced arthritis (CIA) in mice or in synovial tissue of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Arthritic limbs from 30 immunized C57Bl/6J mice were collected at distinct time points covering all stages of the disease. Sections of mouse limbs and synovial tissue samples obtained from 13 OA and 12 RA patients were stained for tyrosine hydroxylase, the key enzyme for catecholamine synthesis (noradrenergic fibers), and for vesicular acetylcholine transporter (cholinergic fibers) by immunohistochemistry. In mouse joint sections, an increase in the ratio of cholinergic to adrenergic nerve fibers appeared at day 35 after immunization. Most of the nerve fibers were located in joint-adjacent skin or muscle tissue, and only few were detected in synovial tissue or in the erosion. In human tissue sections, we were able to show cholinergic fibers in the synovium of one OA patient. These results suggest that cholinergic innervation in the joint region might be upregulated under inflammatory conditions.