Objectives: Some neuropeptides are thought to be involved in modulation of the inflammatory process of arthritis. We studied to elucidate the expression of neuropeptides, substance P (SP) and calcitonin gene-related peptide (CGRP), in synovial tissue taken from the temporomandibular joint (TMJ) with symptomatic internal derangement (ID), and to discuss the relationship between these neuropeptides and joint pain. Methods: Using an immunohistochemical technique, 54 joints in 54 patients were examined. As controls, synovial tissue specimens from 10 joints in 8 subjects with habitual dislocation without pain were also examined. The labeling index (LI) for SP and CGRP-positive cells were calculated as the percentage of immuno-positive cells in each specimen. For statistical analysis, p values of less than 0.05 were considered significant. Results: SP-immuno-positive cells were found mainly in the blood vessels beneath the lining cells in 47 of the 54 joints (87%) with ID, and in 5 of the 10 control specimens. In all of the ID and control specimens, CGRP-immuno-positive cells were observed in the connective tissues around the blood vessels beneath the lining cells. In the ID group, the mean±SD (median) LI for SP and CGRP was 22.5±18.9 (20) and 50.0±26.0 (50) respectively, which was significantly higher (SP: p=0.02, CGRP: p=0.01) than that in controls (6.8±11.2 (3) and 28.0±18.0 (30) respectively). The LI for CGRP was significantly correlated with joint pain (p= 0.04, r=0.30), although SP was not significantly correlated with pain (p= 0.75, r=0.01). Conclusion: These results suggest that these neuropeptides are increased in the inflamed synovial tissues in patients with ID, and that CGRP might play an important role in the mechanism of pain production in patients with symptomatic ID.

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