Peripheral inflammation increases Scya2 expression in sensory ganglia and cytokine and endothelial related gene expression in inflamed tissue.

The sensation of pain (nociception) is a critical factor in host defense during tissue injury and inflammation and is initiated at the site of injury by activation of primary afferent C-fiber and A- partial differential nerve endings. Inflammation induces tissue alterations that sensitize these nociceptive nerve terminals, contributing to persistent pain. To understand this 'algesic tissue environment' and peripheral nervous signaling to the CNS and immune system, we examined cytokine and endothelial-related gene expression profiles in inflamed rat tissues and corresponding dorsal root ganglia (DRG) by microarray and RT-PCR following hind paw injection of carrageenan. In inflamed tissue, forty-two cytokine and endothelial-related genes exhibited elevated expression. In contrast, in DRG, only Scya2 (chemokine C-C motif ligand 2) mRNA was up-regulated, leading to an increase in its gene product monocyte chemoattractant protein-1. Scya2 mRNA was localized by in situ hybridization-immunocytochemical double-labeling to a subpopulation of vanilloid receptor-1 (transient receptor potential vanilloid subtype 1) containing neurons, and its expression was increased by direct transient receptor potential vanilloid subtype 1 stimulation with the vanilloid agonist resiniferatoxin, indicating sensitivity to nociceptive afferent activity. Our results are consistent with the idea that monocyte chemoattractant protein-1 at the site of peripheral injury and/or in DRG is involved in inflammatory hyperalgesia.