Lower density of synovial nerve fibres positive for calcitonin gene-related peptide relative to substance P in rheumatoid arthritis but not in osteoarthritis

Objectives. Sensory nerve fibres (NFs) contain two major neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP). The pro-inflammatory role of SP is known, while CGRP has anti-inflammatory activities by inhibiting T helper type 1 cytokines, TNF secretion and leucocyte proliferation. We demonstrated the increase of SP-positive NFs in RA as compared with OA. This study investigated the density of CGRP-positive NFs relative to SP-positive NFs or sympathetic NFs in synovial tissue of patients with RA and OA. Methods. By immunofluorescent staining of synovial tissue of 25 patients with RA and 35 patients with OA, NFs positive for CGRP, SP and tyrosine hydroxylase (sympathetic NFs) were quantified. Results. Density of CGRP-positive NFs was higher in OA than in RA, and density of SP-positive NFs tended to be higher in RA. In RA patients, comparison of CGRP-positive and SP-positive NFs in the same synovial tissue demonstrated less CGRP-positive than SP-positive NFs. The ratio of CGRP-positive NFs to SP-positive NFs was lower in RA as compared with OA. In OA, but not in RA, density of CGRP-positive NFs positively correlated with density of sympathetic NFs, which is much lower in RA patients. Conclusion. The preponderance of SP-positive NFs over CGRP-positive NFs or sympathetic NFs most probably supports the pro-inflammatory process in patients with RA. The reasons for the loss of CGRP in sensory NFs are not known.