• K W Marshall, E Theriault, and D A Homonko.
• Department of Surgery, University of Toronto, Ontario, Canada. marshall@playfair.utoronto.ca
• J Rheumatol. 1997 Sep 1; 24 (9): 1765-8.

ObjectiveTo investigate the effect of the neuropeptide depleting agent capsaicin on neuropeptides in both synovial and nonsynovial articular tissues and on the relative degree of joint inflammation in established antigen induced arthritis (AIA).MethodsAIA was created in both knees in 3 cats. Once AIA was established, the left knee of each animal received a single 0.5 ml injection of capsaicin (0.3 mg/ml). Three days later, the knees were harvested and dissected into 11 regions. Eleven articular cartilage tissues from both the experimental (capsaicin) and control (non-capsaicin) knees were examined for the immunocytochemical presence of substance P (SP) and calcitonin gene related peptide (CGRP). Additionally, the synovium was examined to determine the severity of joint inflammation.ResultsNerve fibers immunoreactive for SP or CGRP were found in all 11 tissues in each of the non-capsaicin treated AIA knees. Both perivascular and "free" SP and CGRP immunoreactive fibers were present in all 11 articular structures. In the knees treated with capsaicin, however, 48% of the joint tissues examined completely lacked SP immunoreactivity, while 12% had no CGRP immunoreactivity. Inflammatory disease severity was not ameliorated by the single intraarticular injection of capsaicin used in this study.ConclusionThese data indicate that SP and CGRP immunoreactivity is maintained in synovial and nonsynovial articular tissues of non-capsaicin treated knees during subacute joint inflammation. In the capsaicin treated AIA knees, however, there was partial neuropeptide depletion. Nerve fibers containing SP were more sensitive to the peptide depleting effects of capsaicin than were CGRP positive fibers. Depletion of SP and CGRP from some joint tissues did not correlate with a decrease in joint inflammation. Studies incorporating a broad range of dosages will be required to determine whether intraarticular treatment with capsaicin can effectively deplete neuropeptides and thereby ameliorate established inflammatory arthritis.

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