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

采用伊里扎洛夫式固定装置，长期压迫大鼠尾部，形成组织学上的椎间盘退变。椎板部分切除术后，在左侧L4和5神经根上置换尾椎间盘髓核，该装置应用8周。机械痛觉过敏是一种与疼痛相关的行为，在压缩髓核组织治疗的大鼠中观察到比正常椎间盘治疗的大鼠更大，持续时间更长。免疫组化研究显示，髓核内磷脂酶A_2、白细胞介素-1β、肿瘤坏死因子-α、白细胞介素- 8、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。在大鼠的髓核中，观察到较低的pH值，其中仪器应用于尾部4周或8周，而不是12周。用机械压缩椎间盘髓核治疗4周或8周的大鼠，与用正常髓核或压缩髓核治疗12周的大鼠相比，痛觉过敏的程度更大，持续时间更长。总的来说，这些发现表明，椎间盘慢性和机械压迫引起的退行性髓核加重疼痛，这种加重与化学因素（如较低的pH值）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引入大鼠尾部髓核细胞。细胞在选定的基因蛋白（G4-18）培养液中孵育一周后取出。将细胞注射到机械压迫尾部产生的退变椎间盘，蛋白聚糖、胶原蛋白和DNA含量无明显变化。提示将OP-1基因引入椎间盘对椎间盘退变具有保护作用。此外，OP-1作用于髓核组织，控制椎间盘退变过程，如降低pH值，减少疼痛相关行为。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 The cells were withdrawn after incubation in selected culture involved geneticin (G4-18) for one week.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