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Studies in~a new pain control by spinorphin, an endogenous factor : Changes in level of spinorphin and dipeptidyl peptidase III in cerebrospinal fluid from patients with pain

Research Project

Project/Area Number 14572172
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionTokyo Metropolitan Organization of Medical Science

Principal Investigator

YAMAMOTO Yukio  Tokyo Metropolitan Organization of Medical Science, Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 主任研究員 (80124501)

Co-Investigator(Kenkyū-buntansha) HAZATO Tadahiko  Tokyo Metropolitan Organization of Medical Science, Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 副参事研究員 (60109949)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsSpinorphin / Pan / Dipeptidyl peptidase III / Endogenous peptide / EIA
Research Abstract

Spinorphin (LVVYPWT), an endogenous bioactive peptide purified from the spinal cord, demonstrates a nociceptive effect on bradykinin-induced pain in the rat and inhibitory activity against carrageenan-induced neutrophil accumulation in the mouse model of acute inflammation. To further clarify its physiological role in pain and inflammation, we established a method to quantify spinorphin in human cerebrospinal fluid (CSE) and analyzed the relation between its level and the physiological state. First, a specific and sensitive competitive enzyme immunoassay (EIA) was developed with an anti-rabbit spinorphin antibody. Cross-reactivity of the specific antibody with spinorphin analogues was not significant, suggesting that the EIA was specific to spinorphin. Next, levels of spinorphin measured in CSFs derived from patients with various types of pain other than cancer pain were higher in the pain group than in the controls (patients with pain-free and noninflammatory disease of the central nervous system) (21.4±8.2 ng/ml, n=48 vs 8.61±4.4 ng/ml, n=28,P<0.05). Furthermore, the activity of several spinorphin-processing enzymes that regulate some types of pain was examined. The activity of dipeptidyl peptidase III (DPPIII) in CSFs of the pain group was lower than that in the control (1.40±0.65 vs 2.05±0.88 pmol/30 min/100μ1,P<0.05). Interestingly, a statistical correlation was observed between the increase of spinorphin levels and the decrease of DPPIII (r=-0.514,P<0.05). These results indicate that the level of spinorphin may, through the regulatory effect of enzymes, be an indicator of the pathophysiological state.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yamamoto, Y., et al.: "Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes : Roles in pain and inflammation"Current Protein and Peptide Sciences. 3・6. 587-599 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hazato, T., et al.: "A new pain regulated substance spinorphin from spinal cord,"Jpn.J.Pharmacol.. 88 Suppl.1. 138 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 佐藤洋, その他: "脳脊髄液中におけるエンケファリン代謝酵素dipeptidyl peptidase (DPPIII)の動態"麻酔. 52・3. 257-263 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimamura, M, et al.: "A hypoxia-dependent nitroimidzole KIN-841 inhibits angiogenesis by blocking production of angiogenic factor."Brit.J.Cancer. 88・2. 307-313 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Oshizawa T., et al.: "Possible involvement of optimally phosphorylated L-plastin in activation of superoxide-generating NADPH oxidase."J.Biochem.. 134・6. 827-834 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 羽里忠彦, その他: "食肉に関する助成研究調査成果報告書。ウシ脊髄由来の新しい生理活性物質・Spinorphinの研究"伊藤記念財団. 5 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto, Y., Ono, H., Ueda, H., Shimamura, M., Nishimura, K., Hazato, T.: "Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes : Roles in pain and inflammation."Current Protein and Peptide Sciences. 3. 587-599 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 羽里忠彦, 山本行男, 島村眞里子: "平成14年度食肉に関する助成研究調査成果報告書:ウシ脊髄由来の新しい疼痛制御物質・spinorphinの研究"(伊藤記念財団). 第21巻. 278-281 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 佐藤洋, 木村光兵, 山本行男, 羽里忠彦: "脳脊髄液中におけるエンケファリン代謝酵素dipeptidyl peptidase (DPPIII)の動態"麻酔. 第52巻. 257-263 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hazato, T., Yamamoto, Y., Shimamura, M., Takayama, T., Nishimura, K., Ueda, H.: "A new pain regulated substance spinorphin from spinal cord."Jpn.J.Pharmacol.. 88,Suppl.1. 138 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimamura, M., Nagasawa, H., Ashino, H., Yamamoto, Y., Hazato, T., Uto, Y., Hori, H., Inayama, S.: "A hypoxia-dependent nitroimidzo ;le KIN-841 inhibits angiogenesis by blocking production of angiogenic factor."Brit.J. Cancer. 88. 307-313 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 羽里忠彦, 山本行男, 島村眞里子: "平成15年度食肉に関する助成研究調査成果報告書:ウシ脊髄由来の新しい生理活性物質・spinorphinの研究"食肉に関する研究調査成果報告書(伊藤記念財団). 第21巻. 278-281 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Osizawa, T., Yamaguchi, T., Suzuki, K., Yamamoto, Y., Hayakawa, T.: "Possible involvement of optimally phosphorylated L-plastin in activation of superoxide-generating NADPH oxides."J.Biochem.. 134. 827-834 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 佐藤洋, その他: "脳脊髄液中におけるエンケファリン代謝酵素dipeptidyl peptidase(DPPIII)の動態"麻酔. 52・3. 257-263 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimamura, M., et al.: "A hypoxia-dependent nitroimidazole KIN-841 inhibits angiogenesis by blocking production of angiogenic factor."Brit.J.Cancer. 88・2. 307-313 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Oshizawa et al.: "Possible involvement of optimally phosphorylated L-plastin in activation of superoxide-generating NADPH oxidase."J.Biochem. 134・6. 827-834 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 羽里忠彦, その他: "食肉に関する助成研究調査成果報告書。ウシ脊髄由来の新しい生理活性物質・Spinorphinの研究"伊藤記念財団. 5 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamamoto, Y., et al.: "Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes : Roles in pain and inflammation"Current Protein and Peptide Sciences. 3,(6). 587-599 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hazato, T. et al.: "A new pain regulated substance ・ spinorphin from spinal cord"Jpn. J. Pharmacol.. 88 Suppl.1. 138 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimamura, M., et al.: "A hypoxia-dependent nitroimidazole KIN-841 inhibits angiogenesis by blocking production of angiogenic factor"Brit. J. Cancer. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] 佐藤洋, その他: "脳脊髄液中におけるエンケファリン代謝酵素dipeptidyl peptidase III (DPPIII)の動態"麻酔. (印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 羽里忠彦, その他: "食肉に関する助成研究調査成果報告書。ウシ脊髄由来の新しい生理活性物質・spinorphinの研究"伊藤記念財団. 4 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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