Activation of spinal microglia and macrophages in a rat model of stenosis of the lumbar spinal canal

Abstract

Compression of the cauda equina by spinal stenosis is an important clinical problem associated with intermittent claudication and numbness. Previous studies suggest that ischemic changes in the peripheral nerves by compression of cauda equina are the main pathological causes of the disease. It has recently been shown that spinal microglia plays an important role in the central mechanisms of nociception in models of neuropathic pain. In this study, we investigated the pathological changes in spinal microglia and macrophages in a rat model of stenosis of the lumbar spinal canal with and without subsequent decompression. The animals were divided into three groups, sham control, spinal stenosis, and spinal stenosis with decompression. For spinal stenosis, two square pieces of silicon were surgically inserted in the epidural space of the fourth and sixth lumbar segments of the spine (Sekiguchi et al., 2004). In the rats in the decompression group, the silicon inserts were removed at 3 weeks after the initial surgery. At 6 weeks after initial surgery, the animals were sacrificed and the L5 segment of the spinal cord was cut and stained for the markers for activated microglia and macrophages Iba1, ED1 and nuclear factor kappaB (NF kappaB), using multiple-label immunofluorescence. Most Iba1-positive microglia and Iba1/ED1-positive macrophages were found in the dorsal columns; the majority of Iba1-positive cells also expressed NF kappaB. The number of activated microglia and macrophages was significantly larger in rats in the spinal stenosis group than in the sham group. Moreover, this increase was significantly smaller in rats in the decompression group than in the spinal stenosis group. These results suggested that compression of the cauda equina may result in activation of microglia and macrophage in dorsal column.