Gene Expression Profile of Dorsal Root Ganglion in a Lumbar Radiculopathy Model

Abstract

DNA array analysis of dorsal root ganglion (DRG) using a rat model with nerve root constriction. To determine the molecular changes in the DRG adjacent to the injured nerve root in a lumbar radiculopathy model. DNA array analysis in lumbar radiculopathy model has so far focused on the spinal dorsal horn. The molecular changes in the DRG adjacent to the injured nerve root in lumbar radiculopathy remain to be determined. Bilateral L5 DRGs were removed from 12 Sprague-Dawley rats on days 2, 7, 14, and 21 after nerve root ligation and on day 7 from 3 rats with sham operation. The aRNAs from the DRGs with nerve root ligation were labeled with Cy5 dye and those from the opposite side DRG (control) were labeled with Cy3 dye, and then hybridized to a 7793-spot Panorama Micro Array. It was considered to be significantly upregulated, when an average expression ratio of Cy5 to Cy3 was 2 or more. Genes upregulated were classified into early phase group (upregulated on day 2), midphase group (upregulated on days 7 and 14), and continuous group (upregulated from day 2 to 21). Seventeen genes were subjected to validation analysis with real-time quantitative PCR. There were 16 upregulated genes in the early phase group, 56 genes in the midphase group, and 17 genes in the continuous group. Functional categorization revealed dominantly upregulated gene categories in each group; transcription/translation in the early phase group, enzyme/metabolism in the midphase group, and structure in the continuous group. Validation analysis of 17 genes demonstrated mean relative expression of 2.0 or more in all but 1 gene in the DRGs with nerve root ligation and none of them in the DRGs with sham operation. The genes identified in this study, especially those involved in pain signaling and inflammation, serve as potential targets for molecular-based therapy for lumbar radiculopathy.