Gene Expression Changes in Dorsal Root Ganglion of Rat Experimental Lumber Disc Herniation Models

Abstract

Comprehensive overviews of gene expression changes in dorsal root ganglion (DRG) were obtained using microarrays in 2 rat models of experimental lumbar disc herniation (LDH). To clarify the mechanisms of painful radiculopathy caused by LDH from the viewpoint of gene expression changes in DRG of 2 rat models of LDH. Mechanical compression and chemical irritation are considered to be the 2 major causative factors of radiculopathy associated with LDH. Several basic studies have revealed histologic and functional changes in the nerve root and DRG induced by mechanical compression or application of nucleus pulposus. However, the effects of the 2 major factors have not been investigated in detail. METHODS.: The effects of mechanical and chemical factors were assessed in 2 models and in sham-operated rats. The mechanical compression model had a stainless steel rod inserted through a drill hole in the L5 lamina; the nucleus pulposus model had autologous nucleus pulposus placed in the drill hole, and only a drill hole was made in the L5 lamina of sham-operated rats. Samples from the left L5 DRG were harvested from the models with mechanical allodynia and from sham rats and analyzed using microarrays at 3 and 7 days after surgery. The gene expression profiles differed in the 2 models at 7 days, but were similar at 3 days after surgery. Expression of the growth factor gene, insulin-like growth factor 1, and of the cyclinD1, cell division cycle 2 homolog A, and cyclinA2 genes related to the cell cycle was significantly upregulated in the DRG of the mechanical compression group at 7 days after surgery. Mechanical and chemical factors caused altered gene expression in the DRG at 7 days after surgery, suggesting that the mechanisms of nerve injury induced by these factors differ. The upregulation of IGF-1 might be a key factor in painful radiculopathy induced by mechanical factors.