Abstract
Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide implicated in inflammatory diseases involving trigeminal ganglion nerve activation. Within trigeminal ganglia, satellite glia and Schwann cells are found in close association with neuronal cell bodies and fibers, respectively, and are known to express functional CGRP receptors. The goal of this study was to use array analysis to provide a more comprehensive understanding of CGRP regulation of inflammatory proteins and genes in trigeminal glia. Primary trigeminal ganglia cultures enriched for glia were treated with 500 nM CGRP for 8 or 24h. CGRP caused a >3-fold increase in the level of 19 cytokines 8h after CGRP treatment and the levels of each of these cytokines remained significantly elevated over basal unstimulated levels at 24h. While mRNA levels of many genes involved in mitogen-activated protein (MAP) kinase signaling were increased 8h after CGRP treatment, the number of responsive genes was greatly increased at 24h. Specifically, CGRP was shown to temporally regulate expression of multiple MAP kinases as well as numerous MAP kinase-responsive genes including transcription factors, scaffold/anchoring proteins, and cell cycle proteins. Thus, our data provide evidence of an emerging role of CGRP as an important modulator of trigeminal ganglion glia by stimulating cytokine release as well as inducing expression of a diverse array of proteins involved in MAP kinase signaling.