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 derivative 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.