TY - JOUR
T1 - Expression of DRG candidate pain molecules after nerve injury - A comparative study among five inbred mouse strains with contrasting pain phenotypes
AU - Persson, Anna Karin
AU - Xu, Xiao Jun
AU - Wiesenfeld-Hallin, Zsuzsanna
AU - Devor, Marshall
AU - Fried, Kaj
PY - 2010/3
Y1 - 2010/3
N2 - 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 Nav 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 Nav 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.
AB - 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 Nav 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 Nav 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.
KW - Morphology
KW - Neuropathic pain
KW - Pain genetics
KW - Sodium channels
KW - TRP channels
UR - http://www.scopus.com/inward/record.url?scp=77649268464&partnerID=8YFLogxK
U2 - 10.1111/j.1529-8027.2010.00249.x
DO - 10.1111/j.1529-8027.2010.00249.x
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C2 - 20433603
AN - SCOPUS:77649268464
SN - 1085-9489
VL - 15
SP - 26
EP - 39
JO - Journal of the Peripheral Nervous System
JF - Journal of the Peripheral Nervous System
IS - 1
ER -