Overexpression of NGF or GDNF alters transcriptional plasticity evoked by inflammation

Pain. 2005 Feb;113(3):277-84. doi: 10.1016/j.pain.2004.10.025.

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Disease Models, Animal
  • Freund's Adjuvant / adverse effects*
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / physiology
  • Glial Cell Line-Derived Neurotrophic Factor
  • Hyperalgesia / chemically induced
  • Hyperalgesia / etiology
  • Hyperalgesia / metabolism*
  • Inflammation / chemically induced
  • Inflammation / complications
  • Inflammation / metabolism*
  • Mice
  • Mice, Transgenic
  • Nerve Growth Factor / genetics
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • RNA, Messenger / metabolism
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Skin / innervation
  • Skin / physiopathology
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • TRPC Cation Channels
  • Time Factors

Substances

  • Calcium Channels
  • Gdnf protein, mouse
  • Glial Cell Line-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Opioid
  • Sodium Channels
  • TRPC Cation Channels
  • Freund's Adjuvant
  • Nerve Growth Factor