Overexpression of NGF or GDNF alters transcriptional plasticity evoked by inflammation.

Abstract

Transcriptional changes evoked in nociceptive sensory neurons by inflammatory injury play a substantial role in the generation of and recovery from painful hypersensitivity. Transgenic mice overexpressing nerve growth factor (NGF) or glial cell line-derived neurotrophic factor (GDNF) in the skin possess a greatly increased number of nociceptors. Surprisingly, NGF-overexpressers display reduced hypersensitivity and recovered more rapidly in response to inflammation, suggesting a compensatory suppression of nociceptive transmission in these mice. To determine whether these transgenic mice show changes in inflammation-evoked transcriptional plasticity, we examined the expression of a panel of genes implicated in nociceptive signaling in response to injection of complete Freund's adjuvant into the hindpaw. Relative mRNA levels were quantified 1, 4 and 15 days after injection using real-time PCR. In wild type mice CFA injection elicited a reproducible pattern of altered gene expression that returned to baseline over a 2-week period. In mice overexpressing NGF or GDNF the expression patterns for several genes were substantially altered; these changes in injury-evoked patterns of gene expression suggest the existence of endogenous regulatory mechanisms that can compensate for increased nociceptive input by modulating the expression of a limited subset of genes.