Dorsal horn-enriched genes identified by DNA microarray, in situ hybridization and immunohistochemistry.
BACKGROUND
Neurons in the dorsal spinal cord play important roles in nociception and pain. These neurons receive input from peripheral sensory neurons and then transmit the signals to the brain, as well as receive and integrate descending control signals from the brain. Many molecules important for pain transmission have been demonstrated to be localized to the dorsal horn of the spinal cord. Further understanding of the molecular interactions and signaling pathways in the dorsal horn neurons will require a better knowledge of the molecular neuroanatomy in the dorsal spinal cord.


RESULTS
A large scale screening was conducted for genes with enriched expression in the dorsal spinal cord using DNA microarray and quantitative real-time PCR. In addition to genes known to be specifically expressed in the dorsal spinal cord, other neuropeptides, receptors, ion channels, and signaling molecules were also found enriched in the dorsal spinal cord. In situ hybridization and immunohistochemistry revealed the cellular expression of a subset of these genes. The regulation of a subset of the genes was also studied in the spinal nerve ligation (SNL) neuropathic pain model. In general, we found that the genes that are enriched in the dorsal spinal cord were not among those found to be up-regulated in the spinal nerve ligation model of neuropathic pain. This study also provides a level of validation of the use of DNA microarrays in conjunction with our novel analysis algorithm (SAFER) for the identification of differences in gene expression.


CONCLUSIONS
This study identified molecules that are enriched in the dorsal horn of the spinal cord and provided a molecular neuroanatomy in the spinal cord, which will aid in the understanding of the molecular mechanisms important in nociception and pain.
Department of Molecular Pharmacology, Merck Research Laboratories, West Point, PA 19486, USA. hong_sun@merck.com
Hong
H
Sun
Jian
J
Xu
Kimberly B
KB
Della Penna
Robert J
RJ
Benz
Fumi
F
Kinose
Daniel J
DJ
Holder
Kenneth S
KS
Koblan
David L
DL
Gerhold
Hao
H
Wang
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008026:Ligation; D008297:Male; D009408:Nerve Compression Syndromes / Q000150:complications / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D010146:Pain / Q000209:etiology; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology*