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

Research Project

Project/Area Number 13671536
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionWakayama Medical University, School of Medicine

Principal Investigator

KAWAKAMI Mamoru  Wakayama Medical University, Department of Orthopedic Surgery, Assistant Professor, 医学部・整形外科学, 講師 (20195051)

Co-Investigator(Kenkyū-buntansha) TAMAKI Tetsuya  Wakayama Medical University, Department of Orthopedic Surgery, Chairman & Professor, 医学部・整形外科学, 教授 (30009592)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
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)
Keywordsnucleus pulposus / degeneration / nerve root / hyperalgesia / chemokine / tumor necrosis factor / pH / osteogenic protein-1 / 椎間板 / 髄核 / 痛感過敏 / 椎間板変性 / 疼痛 / 痛覚過敏 / phospholipase A_2 / interleukin-1β / tumor necrosis factor-α
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, … 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

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (15 results)

All Other

All Publications (15 results)

  • [Publications] 川上 守 ほか: "機械的圧迫後の障害椎間板の髄核に起因する神経因性疼痛"日本整形外科学会誌. 75. S884 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mamoru Kawakami, et al.: "Comparison of neuropathic pain induced by application of normal and mechanically compressed nucleus pulposus to the lumbar nerve roots in the rat"Transaction of Orthopedic Research Society. 27. 302 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 川上 守ほか: "腰髄神経根への変性髄核留置による神経因性疼痛の増強"日本整形外科学会誌. 76. S1038 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mamoru Kawakami, et al.: "Neuropathic pain enahnced by degenerative nucleus pulposus in the rat"Transaction of Orthopedic Research Society. 28. 1144 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami M, et al.: "Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to the lumbar nerve roots in the rat"J Orthop Res. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mamoru Kawakami, Hiroshi Hashizume, Hideto Nishi, Takuji Matsumoto, Tetsuya Tamaki, Koichi Kuribayashi: "Comparison of neuropathic pain induced by application of normal and mechanically compressed nucleus pulposus to the lumbar nerve roots in the rat"Transaction of Orthopedic Research Society. 27(1). 302 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mamoru Kawakami, Tetsuya Tamaki, Hiroshi Hashizume, Takuji Matsumoto, Koichi Kuribayashi: "Neuropathic pain enhanced by degenerative nucleus pulposus in the rat"Transaction of Orthopedic Research Society. 28(2). 1144 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawakami M, Hashizume H, Nishi H, Matsumoto T, Tamaki T, Kuribayashi K: "Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat"J Orthop Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 川上 守ほか: "機械的圧迫後の障害椎間板の髄核に起因する神経因性疼痛"日本整形外科学会誌. 75(8). S884 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mamoru Kawakami et al.: "Comparison of neuropathic pain induced by application of normal and mechanically compressed nucleus pulposus to the lumbar nerve roots in the rat"Transaction of Orthopaedic Research Society. 27(1). 302 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 川上 守ほか: "腰髄神経根への変性髄核留置による神痙因性疼痛の増強"日本整形外科学会誌. 76(8). S1038 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mamoru Kawakami et al.: "Neuropathic pain enhanced by degenerative nucleus pulposus in the rat"Transaction of Orthopedic Research Society. 28(2). 144 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mamoru Kawakami et al.: "Comparison of neuropathic pain induced by application of normal and mechanically compressed nucleus pulposus to the lumbar nerve roots in the rat"J Orthop Res. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 川上 守ほか: "機械的圧迫後の障害椎間板の髄核に起因する神経因性疼痛"日本整形外科学会誌. 75(8). S884 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mamoru Kawakami et al.: "Comparison of neuropathic pain induced by application of normal and mechanically compressed nucleus pulposus to the lumbar nerve roots in the rat"Transaction of Orthopedic Research Society. 27(1). 302 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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