Overexpression of NGF or GDNF alters transcriptional plasticity evoked by inflammation.
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.
Molliver
Derek C
DC
Department of Medicine, University of Pittsburgh Medical Center, S841 Scaife, Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Lindsay
Jessica
J
Albers
Kathryn M
KM
Davis
Brian M
BM
D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006930:Hyperalgesia / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000294:innervation / Q000503:physiopathology; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D050052:TRPC Cation Channels; D013997:Time Factors
D015220:Calcium Channels; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D011957:Receptors, Opioid; D015222:Sodium Channels; D050052:TRPC Cation Channels; D005620:Freund's Adjuvant; D020932:Nerve Growth Factor