Osteogenic protein-1 gene transfer can protect disc degeneration induced by chronic mechanical compression that enhances a pain-related behavior

用Ilizarov型装置固定并长期压迫大鼠的尾巴，造成椎间盘退变的组织学改变。于左侧L4和L5神经根行部分椎板切除后，取取自尾盘的髓核，置入髓核8周。在接受压缩髓核组织治疗的大鼠中，观察到的机械性痛觉过敏是一种与疼痛相关的行为，而且持续时间比接受正常髓核组织治疗的大鼠更严重，持续时间更长。免疫组织化学研究表明，髓核内磷脂酶A2、白介素1β、肿瘤坏死因子α、白介素8和单核细胞趋化蛋白1等生物活性物质与机械性痛觉过敏的增强无关。在尾部应用该装置4或8周，而不是12周，在大鼠髓核内观察到较低的pH。老鼠，…与正常或压迫髓核12周的大鼠相比，更多的大鼠接受了4周或8周的机械加压髓核治疗，表现出更严重和更长时间的痛觉过敏。总而言之，这些发现表明，由慢性和机械压迫椎间盘引起的退行性髓核增强了疼痛，并且这种增强与诸如较低的pH等化学因素有关，而与上述生物活性物质无关。另一方面，将成骨蛋白-1(OP-1)基因pW24导入大鼠尾部髓核细胞。在含有G4-18的精选培养物中孵育一周后取出细胞。将细胞注射到由机械压迫尾部造成的退变的椎间盘中，蛋白多糖、胶原蛋白和DNA含量没有明显变化。这些结果提示，将OP-1基因导入到椎间盘中可以保护椎间盘退变。此外，OP-1作用于髓核组织，控制诸如较低的pH值等椎间盘退变过程，并减少疼痛相关行为。较少

An llizarov-type apparatus was used for immobilization and chronically applied compression of the rat's tail to produce disc degeneration histologicaliy. The nucleus pulposus obtained from the tail intervertebral disc, in which the apparatus was applied for eight weeks, was replaced on left L4 and 5 nerve roots after partial laminectomy. Mechanical hyperalgesia, a pain-related behavior, observed in rats treated with the compressed nucleus pulposus tissue was greater and of longer duration than in the rats treated with normal discs. Immunohistochemical studies demonstrated that there were no relationships between enhancement of the mechanical hyperalgesia and bioactive substances such as phospholipase A_2, interleukin-1β, tumor necrosis factor-α, interleukin- 8, and monocyte chemotactic protein-1 in the nucleus pulposus. A lower pH in the nucleus pulposus was observed in the rat, in which the apparatus was applied to the tail for four or eight weeks, but not for twelve weeks. The rats, … More which were treated by the nucleus pulposus obtained from mechanically compressed intervertebrai disc for four or eight weeks, showed evidence of greater and of longer duration hyperalgesia, compared with the rats treated with normal or compressed nucleus pulposus for twelve weeks. Collectively, these findings suggest that degenerative nucleus pulposus, which is induced by chronic and mechanical compression to the intervertebral disc, enhances pain, and that the enhancement is related to chemical factors such as a lower pH, but not bioactive substances described above. On the other hand, pW24, which is an osteogenic protein-1 (OP-1) gene, was introduced to the nucleus pulposus cells in the rat's tail. The cells were withdrawn after incubation in selected culture involved geneticin (G4-18) for one week. Injection of the cells to the degenerated intervertebral disc, which was produced by mechanical compression to the tail, resulted in not significant changes of proteoglycans, collagens and DNA contents. These results suggest that OP-1 gene introduction to the intervertebral disc can protect disc degeneration. In addition, OP-1, which acts in the nucleus pulposus tissue, controls the process of disc degeneration such as a lower pH and reduces pain-related behaviors. Less