| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
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,
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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 The cells were withdrawn after incubation in selected culture involved geneticin (G4-18) for one week.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
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