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.