CAPSAICIN EFFECTS ON SUBSTANCE-P AND CGRP IN RAT ADJUVANT ARTHRITIS

The effects of capsaicin on the sensory neuropeptides substance P and calcitonin gene-related peptide were analyzed in the ankle joints and dorsal root ganglia (L2-L6) of adult female Lewis rats. The study incl uded 23 normal rats and 23 arthritic rats, all injected subcutaneously with capsaicin (total dose 200 mg/kg bw). Another two groups of anima ls from a previous study, i.e.,, 23 normal rats and 23 arthritic rats not given capsaicin served as controls. Adjuvant arthritis was induced by inoculation with heat-killed mycobacteria. The morphological distr ibution of sensory neuropeptides was assessed by immunohistochemistry and the tissue concentrations were determined by radioimmunoassay. In normal rats, capsaicin significantly reduced the concentrations of sub stance P and calcitonin gene-related peptide in ankle joints (54 respe ctively) as well as dorsal root ganglia (40 and 54%, respectively). In arthritic rats those pretreated with capsaicin had significantly lowe r concentrations of substance P and calcitonin gene-related peptide in dorsal root ganglia (19 and 42%, respectively) compared to the arthri tic controls. In the ankle joints, however, only the SP concentration was reduced (42%). Notably, this was accompanied by a 40% reduction in inflammatory response as assessed by comparing the ankle joint weight s of the experimental groups. In general, there was a good correlation between the neuropeptide concentrations in ipsilateral ankle joints a nd the corresponding dorsal root ganglia as assessed in individual rat s. The present study of adjuvant induced arthritis shows that capsaici n administration reduces the otherwise up-regulated levels of sensory neuropeptides in dorsal root ganglia and ankle joints. However, capsai cin at the dose given can only mitigate, not completely prevent the de velopment of joint inflammation. Nonetheless, the findings suggest tha t antineuronal therapy targeted against specific neurotransmitters may prove useful in inflammatory joint disease.