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.