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Molecular mechanisms of disc degeneration and innervation in human discogenic pain

Research Project

Project/Area Number 24592214
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical University

Principal Investigator

ENDO Kenji  東京医科大学, 医学部, 講師 (90266479)

Co-Investigator(Kenkyū-buntansha) SAWAJI Yasunobu  東京医科大学, 医学部, ポストドクター (20571152)
KOSAKA Taiichi  東京医科大学, 医学部, 講師 (10328213)
SUZUKI Hidekazu  東京医科大学, 医学部, 講師 (40317871)
YAMAMOTO Kengo  東京医科大学, 医学部, 教授 (10246316)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords腰痛 / 椎間板変性 / 神経侵入 / 神経成長因子 / 細胞外基質分解酵素 / 非ステロイド性抗炎症薬 / プロスタグランジン / MMP / NSAIDs / prostaglandin / NGF / Prostaglandin
Outline of Final Research Achievements

Degeneration of the intervertebral disc (IVD) by metalloproteinases and following innervation of the sensory nerve fiber, which is dependent on nerve growth factor (NGF), is considered as one of the mechanisms of developing discogenic pain. Although selective COX-2 inhibitors are recommended and used for the conservative treatment of low back pain, their effects on metalloproteinases and NGF expressions were unclear.
The effects of selective COX-2 inhibitors on the metalloproteinases and NGF expression were investigated in isolated human IVD cells. Selective COX-2 inhibitors exaggerated the expressions of both metalloproteinases and NGF induced by IL-1. These results suggest that, although selective COX-2 inhibitors are effective for inflammatory pain, they might not be effective or could even accelerate the disc degeneration and nerve innervation.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (18 results)

All 2015 2014 2013 2012

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (16 results)

  • [Journal Article] Regulation of nerve growth factor by anti-inflammatory drugs, a steroid, and a selective cyclooxygenase 2 inhibitor in human intervertebral disc cells stimulated with interleukin-12013

    • Author(s)
      Wukikun Alimasi, Yasunobu Sawaji, Kenji Endo, Makiko Yorifuji, Hidekazu Suzuki, Taiichi Kosaka, Takaaki Shishido, Kengo Yamamoto
    • Journal Title

      Spine

      Volume: 38 Issue: 17 Pages: 1466-1472

    • DOI

      10.1097/brs.0b013e318294edb1

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulation of nerve growth factor by anti-inflammatory drugs, a steroid and a selective COX-2 inhibitor in human intervertebral disc cells stimulated with interleukin-12013

    • Author(s)
      Wuqikun Alimasi, Yasunobu Sawaji, Kenji Endo, Makiko Yorifuji, Hidekazu Suzuki, Taiichi Kosaka, Takaaki Shishido, Kengo Yamamoto
    • Journal Title

      Spine

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] PGE2 negatively regulates NGF expression by inducing DUSP-1 in human intervertebral disc cells2015

    • Author(s)
      Yasunobu Sawaji, Hidekazu Suzuki, Kenji Endo, Hidetoshi Tanaka, Taiichi Kosaka, Kengo Yamamoto
    • Organizer
      The International Society for the Study of Lumbar Spine
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-06-08 – 2015-06-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] PGE2 negatively regulates MMP-1 expression by inducing DUSP-1 in human intervertebral disc cells2015

    • Author(s)
      Makiko Yorifuji, Yasunobu Sawaji, Hidekazu Suzuki, Kenji Endo, Hidetoshi Tanaka, Taiichi Kosaka, Kengo Yamamoto
    • Organizer
      The International Society for the Study of Lumbar Spine
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2015-06-08 – 2015-06-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 椎間板性腰痛に関わる神経成長因子のプロスタグランジンによる発現制御機構2015

    • Author(s)
      澤地恭昇,村田寿馬,鈴木秀和,依藤麻紀子,田中英俊,小坂泰一,山本謙吾
    • Organizer
      第44回 日本脊椎脊髄病学会学術集会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2015-04-16 – 2015-04-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] ヒト椎間板性腰痛における神経成長因子発現調節の分子機構2014

    • Author(s)
      村田寿馬,澤地恭昇,依藤麻紀子,鈴木秀和,遠藤健司,小坂泰一,山本謙吾
    • Organizer
      第12回 整形外科痛みを語る会
    • Place of Presentation
      福岡県久留米市
    • Year and Date
      2014-06-28 – 2014-06-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] A novel pharmacological action of prostaglandin E1 for intervertebral disc degeneration and innervation2013

    • Author(s)
      Yasunobu Sawaji, Wuqikun Alimasi, Kenji Endo, Hidekazu Suzuki, Hidetoshi Tanaka, Kengo Yamamoto
    • Organizer
      International Society for the Study of the Lumbar Spine
    • Place of Presentation
      Arizona, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 椎間板軟骨細胞における神経成長因子発現に対するPGE1の薬理作用2013

    • Author(s)
      村田寿馬,澤地恭昇,遠藤健司,ウチクンアルマス,依藤麻紀子,西村浩輔,鈴木秀和,田中英俊,小坂泰一,山本謙吾
    • Organizer
      第11回 整形外科痛みを語る会
    • Place of Presentation
      郡山市,福島県
    • Related Report
      2013 Research-status Report
  • [Presentation] 腰部脊柱管狭窄症におけるPGE1のMMP/NGFの発現調節2013

    • Author(s)
      村田寿馬,澤地恭昇,遠藤健司,ウチクンアルマス,依藤麻紀子,西村浩輔,鈴木秀和,田中英俊,小坂泰一,山本謙吾
    • Organizer
      第62回 東日本整形災害外科学会
    • Place of Presentation
      北佐久郡,長野県
    • Related Report
      2013 Research-status Report
  • [Presentation] 椎間板軟骨細胞における神経成長因子発現に対するPGE1の新規薬理作用神経成長因子発現に対するPGE1の新規薬理作用2013

    • Author(s)
      村田寿馬,澤地恭昇,遠藤健司,ウチクンアルマス,依藤麻紀子,西村浩輔,鈴木秀和,田中英俊,小坂泰一,山本謙吾
    • Organizer
      第28回 日本整形外科基礎学術集会
    • Place of Presentation
      千葉市,千葉県
    • Related Report
      2013 Research-status Report
  • [Presentation] 椎間板細胞における神経成長因子発現に対するPGE1の新規薬理作用2013

    • Author(s)
      村田寿馬,澤地恭昇,遠藤健司,ウチクンアルマス,依藤麻紀子,西村浩輔,鈴木秀和,田中英俊,小坂泰一,山本謙吾
    • Organizer
      第6回 日本運動器疼痛学会
    • Place of Presentation
      神戸市,兵庫県
    • Related Report
      2013 Research-status Report
  • [Presentation] Roles of PGE2 on the intervertebral disc degeneration and nerve ingrowth in human intervertebral disc cells2012

    • Author(s)
      Wuqikun Alimasi, Yasunobu Sawaji, Dai Kimura, Hidetoshi Tanaka, Taiichi Kosaka, Kenji Endo, Kengo Yamamoto
    • Organizer
      第41回日本脊椎脊髄病学会
    • Place of Presentation
      石橋文化センター,久留米市,福岡県
    • Related Report
      2012 Research-status Report
  • [Presentation] EP1/3 pathway suppresses exaggeration of IL-1-induced collagenases by a selective COX-2 inhibitor in human IVD cells2012

    • Author(s)
      Sawaji Y., Alimasi W., Endo K., Kosaka T., Kimura D. and Yamamoto K.
    • Organizer
      International Society for the Study of the Lumbar Spine
    • Place of Presentation
      Amsterdam, Netherland
    • Related Report
      2012 Research-status Report
  • [Presentation] EP2/4 receptor suppresses the expression of NGF in human IVD cells2012

    • Author(s)
      Alimasi W., Sawaji Y., Kimura D., Tanaka H., Kosaka T., Endo K., Yamamoto K.
    • Organizer
      International Society for the Study of the Lumbar Spine
    • Place of Presentation
      Amsterdam, Netherland
    • Related Report
      2012 Research-status Report
  • [Presentation] 腰椎椎間板変性およびNGF発現とPGE2, EP受容体の関係 ~NSAIDs無効の慢性疼痛機序に関連して~2012

    • Author(s)
      澤地恭昇,ウチクン・アルマス,遠藤健司,山本謙吾
    • Organizer
      第10回 整形外科痛みを語る会 第5回 麻酔科痛みのメカニズムを語る会 合同開催
    • Place of Presentation
      土佐ロイヤルホテル,安芸群,高知県
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト椎間板変性に対する選択的COX-2阻害剤およびPGE2の効果2012

    • Author(s)
      澤地恭昇,ウチクン・アルマス,遠藤健司,田中英俊,小坂泰一,山本謙吾
    • Organizer
      第27回 日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋国際会議場,名古屋,愛知県
    • Related Report
      2012 Research-status Report
  • [Presentation] Roles of PGE2 on the intervertebral disk degeneration and nerve ingrowth in human intervertebral disk cells2012

    • Author(s)
      Wuqikun Alimasi, Yasunobu Sawaji, Dai Kimura, Hidetoshi Tanaka, Taiichi Kosaka, Kenji Endo, Kengo Yamamoto
    • Organizer
      第27回 日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋国際会議場,名古屋,愛知県
    • Related Report
      2012 Research-status Report
  • [Presentation] 腰椎椎間板変性と神経浸潤に対する選択的COX-2阻害剤の効果2012

    • Author(s)
      澤地恭昇,ウチクン・アルマス,遠藤健司,小坂泰一,山本謙吾
    • Organizer
      第5回 日本運動器疼痛学会
    • Place of Presentation
      TFTホール,有明,東京
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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