Neuropeptide gene expression and capsaicin-sensitive primary afferents: maintenance and spread of adjuvant arthritis in the rat.

Abstract

1. Many experimental and clinical arthritides are characterized by their bilateral nature. There is strong evidence to suggest that this bilateral spread may be mediated by a neuronal mechanism. We have previously shown early and sustained induction of mRNAs encoding preprotachykinin (PPT) and calcitonin gene-related peptide (CGRP) in dorsal root ganglion (DRG) neurons innervating an inflamed, arthritic joint. We have now investigated the involvement of capsaicin-sensitive primary afferents and the expression of neuropeptide mRNAs in the maintenance and bilateral spread of mild adjuvant-induced arthritis in the rat. 2. Capsaicin was applied perineurally to either the left (Cap-L) or right (Cap-R) sciatic nerve of halothane-anaesthetized male Han Wistar rats. Two weeks after capsaicin lesioning, arthritis was induced by injection of Freund's complete adjuvant (FCA) around the left ankle at a dose that caused inflammation of the left ankle joint, and a delayed (14 days) contralateral (right) ankle arthritis. Arthritis was monitored for 15 days after injection, when animals were killed and the lumbar DRG dissected. PPT, CGRP, somatostatin (SS), and vasoactive intestinal polypeptide (VIP) mRNA expression was determined in L5 DRG using in situ hybridization. 3. Spread of inflammation/arthritis to the right limb was associated with bilateral rises in PPT and CGRP mRNA expression in L5 DRG. SS mRNA expression in right DRG was unaffected by spread of inflammation. FCA-L+Cap-L reduced left joint swelling and prevented spread of arthritis to the right joint when assessed by joint swelling. This inhibition of spread of arthritis was associated with significant reductions in all left L5 DRG neuropeptide mRNAs compared with controls, and the rise in right L5 DRG PPT mRNA expression seen in FCA-L-alone animals was blocked. FCA-L+Cap-R also reduced left joint swelling and prevented the spread of inflammation to the right ankle. This lesion prevented the rise in PPT and CGRP mRNA expression seen in right DRG with FCA-L alone. 4. These findings suggest a role for capsaicin-sensitive primary afferents and the primary afferent neuropeptides encoded by PPT and CGRP mRNA in the maintenance and spread of arthritis.