Coupling gene chip analyses and rat genetic variances in identifying potential target genes that may contribute to neuropathic allodynia development.
Genetic factors and nerve injury-induced changes of gene expression in sensory neurons are potential contributors to tactile allodynia, a neuropathic pain state manifested as hypersensitivity to innocuous mechanical stimulation. To uncover genes relevant to neuropathic allodynia, we analyzed gene expression profiles in dorsal root ganglia (DRG) of spinal nerve-ligated Harlan and Holtzman Sprague Dawley rats, strains with different susceptibilities to neuropathic allodynia. Using Affymetrix gene chips, we identified genes showing differential basal-level expression in these strains without injury-induced regulation. Of more than 8000 genes analyzed, less than 180 genes in each strain were regulated after injury, and 19-22% of that was regulated in a strain-specific manner. Importantly, we identified functionally related genes that were co-regulated post injury in one or both strains. In situ hybridization and real-time PCR analyses of a subset of identified genes confirmed the patterns of the microarray data, and the former also demonstrated that injury-induced changes occurred, not only in neurons, but also in non-neuronal cells. Together, our studies provide a global view of injury plasticity in DRG of these rat stains and support a plasticity-based mechanism mediating variations in allodynia susceptibility, thus providing a source for further characterization of neuropathic pain-relevant genes and potential pathways.
Valder
Carolina R
CR
Department of Anesthesiology, University of California San Diego, La Jolla, USA.
Liu
Jan-Jan
JJ
Song
Yan-Hua
YH
Luo
Z David
ZD
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D005796:Genes / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D017403:In Situ Hybridization; D008297:Male; D009437:Neuralgia / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010147:Pain Measurement; D016133:Polymerase Chain Reaction; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013127:Spinal Nerves / Q000293:injuries / Q000503:physiopathology