CHANGES IN PREPROTACHYKININ MESSENGER-RNA EXPRESSION AND SUBSTANCE-P LEVELS IN DORSAL-ROOT GANGLIA OF MONOARTHRITIC RATS - COMPARISON WITH CHANGES IN SYNOVIAL SUBSTANCE-P LEVELS

We have measured changes in the expression of gamma-preprotachykinin m RNA and levels of the neuropeptide substance P in the lumbar 4 and 5 d orsal root ganglia at various time points following the induction of a n antigenic monoarthritis in the rat knee. The results were compared w ith changes in substance P levels in the knee joint synovium during ac ute and chronic phases of the disease. On day 3 post-induction, there was a significant increase in the expression of gamma-preprotachykinin mRNA in the dorsal root ganglia. Concomitant with this increase in me ssage was a rise in the levels of substance P in the dorsal root gangl ia. On days 7, 10 and 21, mRNA expression had returned to control valu es whereas ganglion peptide levels were significantly below controls. In contrast there was little change in the total substance P levels in the synovium on days 1 and 3 despite the observed changes in the gang lia. By day 10, however, synovial levels had risen significantly above control values and remained elevated thereafter. Our results show a t ransitory increase in substance P synthesis after induction of an anti genic monoarthritis. This response is not mirrored in the periphery wh ere there is no initial change in total substance P levels perhaps ref lecting increased degradation by enzymes known to be present within in flamed tissue. Paradoxically synovial substance P levels are increased in the latter phases of the model which may serve to modify the infla mmatory response.