Adjuvant-induced joint inflammation causes very rapid transcription of beta-preprotachykinin and alpha-CGRP genes in innervating sensory ganglia

Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in neurogenic inflammation and nociception in experimental and clinical in flammatory arthritis. We examined the very early changes in response to adj uvant injection in a rat model of unilateral tibio-tarsal joint inflammatio n and subsequent monoarthritis. Within 30 min of adjuvant injection ipsilat eral swelling and hyperalgesia were apparent, and marked increases in beta -preprotachykinin-A (beta -PPT-A) and alpha -calcitonin gene-related peptid e (CGRP)-encoding mRNAs were observed in small-diameter L5 DRG neurones inn ervating the affected joint. This response was augmented by recruitment of additional small-diameter DRG neurones expressing beta -PPT-A and CGRP tran scripts. The increased mRNA was paralleled by initial increases in L5 DRG c ontent of the protein products, substance P and calcitonin gene-related pep tide. Within 15 min of adjuvant injection there were increases in electrica l activity in sensory nerves innervating a joint. Blockade of this activity prevented the rapid induction in beta -PPT-A and CGRP mRNA expression in D RG neurones. increased expression of heteronuclear (intron E) beta -PPT-A R NA suggests that increases in beta -PPT-A mRNA levels were, at least in par t, due to transcription. Pre-treatment with the protein synthesis inhibitor cycloheximide had no effect upon the early rise in neuropeptide mRNAs. Thi s and the rapid time course of these changes suggest that increased sensory neural discharge and activation of a latent modulator of transcription are involved.