Expression of DRG candidate pain molecules after nerve injury--a comparative study among five inbred mouse strains with contrasting pain phenotypes.
Neuropathic pain that develops after trauma to a nerve may be caused by altered transcription of genes in the damaged neurons. We have previously investigated the effect of nerve injury on the expression of six dorsal root ganglion (DRG) pain candidate molecules in five inbred mouse strains with different pain phenotypes after nerve injury. In this study, we present a detailed morphological examination of mRNA expression in the DRG in the same mouse strains. For Na(v) 1.9, TRPA1, and TRPM8, the size spectra of labeled neurons remained mostly unchanged after injury in all strains. However, in CBA, AKR, and C58 mice, injury caused a preferential downregulation of Na(v) 1.8 in large diameter neurons. In CBA mice there was a shift toward larger neuronal profiles expressing TRPV1 after injury, indicating de novo (or upregulated) expression of TRPV1 in a subpopulation of neurons that normally does not express this gene. Finally, in C58 mice there was a shift toward smaller P2X3-expressing neuronal profiles after injury, suggesting that a loss of P2X3 mRNA transcript occurred preferentially in medium-sized cells. We used a multivariate statistical model to compare the regulation patterns of the six DRG genes. Clustering patterns suggested that genes of similar phylogenetic origin and function are regulated similarly.
Persson
Anna-Karin
AK
Center for Oral Biology, Novum, Karolinska Institutet, Huddinge, Sweden. anna-karin.persson@yale.edu
Xu
Xiao-Jun
XJ
Wiesenfeld-Hallin
Zsuzsanna
Z
Devor
Marshall
M
Fried
Kaj
K
D000818:Animals; D005163:Factor Analysis, Statistical; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D015999:Multivariate Analysis; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D013127:Spinal Nerves / Q000293:injuries*
D012333:RNA, Messenger