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Elucidation of the mechanism of pain induced by rotator cuff tear and examination of treatment for pain

Research Project

Project/Area Number 18K16633
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionKitasato University

Principal Investigator

KENMOKU Tomonori  北里大学, 医学部, 助教 (00533324)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords腱板断裂 / 運動器疼痛 / 神経成長因子 / シクロオキシゲナーゼ / 疼痛コントロール / 神経ペプチド / 疼痛 / 炎症性サイトカイン / 反復性肩関節脱臼 / 肩腱板断裂 / 疼痛関連物質
Outline of Final Research Achievements

We investigated the mechanism of chronic pain in rotator cuff tears. Synovial tissue was obtained from the subacromial bursa and rotator interval during arthroscopic rotator cuff repair, and NGF, Apelin, and COX-2 were examined using PCR. The control uses synovial tissue from patients with recurrent shoulder dislocation.Although there was no difference in expression of COX-2 compared to the control, NGF was significantly higher. NGF was significantly higher than that in the dislocated group even when Western blot was used. Apelin was also significantly elevated in the human subacromial sac. These are consistent with the results of animal experiments. Therefore, NGF and Apelin could be therapeutic targets for the pain induced by rotator cuff tear.

Academic Significance and Societal Importance of the Research Achievements

腱板断裂は主に変性断裂であり、70代以上の半数以上は腱板断裂を認める。しかし、症候性腱板断裂の割合は36%と言われ、その主訴は疼痛がメインである。そのため疼痛コントロールは治療上重要である。しかし、一般的なNSAIDsは無効であることが多い。今回NSAIDsが無効である理由としてCOX-2が疼痛のメインでないことがわかった。そのため、NSAIDsの漫然とした処方の注意喚起となる。そして、新たな疼痛コントロールのターゲットとしてNGF,Apelinが挙がった。抗NGF抗体は現在腰痛や変形性関節症にも適応がある。腱板断裂に対しても有効性が示唆され、効果があれば手術件数の減少が期待できる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2021 2020 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (9 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Increased nerve growth factor expression in the synovial tissues of patients with rotator cuff tears2021

    • Author(s)
      Ryo Tazawa, Tomonori Kenmoku, Kentaro Uchida, Lars Arendt-Nielsen, Naoshige Nagura, Mitsufumi Nakawaki, Toshihide Matsumoto, Gen Inoue, Hiroto Takeuchi, Takenori Jimbo, Toshiyuki Nakazawa, Michinari Fukuda, Masashi Takaso
    • Journal Title

      Molecular Pain

      Volume: -

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-1β mediates NGF and COX-2 expression through transforming growth factor-activating kinase 1 in subacromial bursa cells derived from rotator cuff tear patients.2019

    • Author(s)
      Nagura N, Uchida K, Kenmoku T, Inoue G, Nakawaki M, Miyagi M, Takaso M.
    • Journal Title

      journal of Orthopaedic Science

      Volume: 24 Issue: 5 Pages: 925-929

    • DOI

      10.1016/j.jos.2019.02.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differential mRNA Expression of COX -2 and Proinflammatory Mediators in Patients with Rotator Cuff Tears and Osteoarthritis of the Hip2019

    • Author(s)
      Kenmoku T, Uchida K, Nagura N, Fujimaki H, Nakawaki M, Takahira N, Fukushima K, Tazawa R, Muneshige K, Inoue G, Takaso M
    • Journal Title

      Open Journal of Orthopedics

      Volume: 9 Issue: 11 Pages: 254-263

    • DOI

      10.4236/ojo.2019.911026

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nerve growth factor continuously elevates in a rat rotator cuff tear model.2019

    • Author(s)
      Nagura N, Kenmoku T, Uchida K, Nakawaki M, Inoue G, Takaso M
    • Journal Title

      J Shoulder Elbow Surg

      Volume: 28 Issue: 1 Pages: 143-148

    • DOI

      10.1016/j.jse.2018.06.030

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three-dimensional full-scale bone modeling for preoperative simulation of surgery in patients with elbow contractures due to bone deformities2017

    • Author(s)
      Nagura Naoshige、Kenmoku Tomonori、Onuma Kenji、Fukushima Kensuke、Fujimaki Hisako、Takahira Naonobu、Takaso Masashi
    • Journal Title

      Clinical Case Reports

      Volume: 5 Issue: 8 Pages: 1401-1406

    • DOI

      10.1002/ccr3.1003

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 加齢に伴う腱板TGF-β産生上昇はapelinの発現を低下させる2020

    • Author(s)
      田澤諒、内田健太郎、見目智紀、名倉直重、中脇充章、宗重響子、松本光圭、井上宏介、石井大輔、高岡純一、髙相晶士
    • Organizer
      第47回日本肩関節学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 加齢に伴う腱板におけるmyokine apelinの発現低下機構の検討2020

    • Author(s)
      田澤諒、内田健太郎、見目智紀、名倉直重、中脇充章、大貫裕子、井上玄、髙相晶士
    • Organizer
      第93回日本整形外科学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 加齢に伴う腱板におけるApelin発現低下と腱板変性の関連2020

    • Author(s)
      田澤諒、内田健太郎、見目智紀、名倉直重、中脇充章、井上玄、髙相晶士
    • Organizer
      第93回日本整形外科学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 反復性肩関脱臼の関節内では軽度の炎症が持続している2020

    • Author(s)
      宗重響子、見目智紀、内田健太郎、名倉直重、中脇充章、田澤諒、井上宏介、松本光圭、髙相晶士
    • Organizer
      第47回日本肩関節学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 腱板断裂後のApelinの発現と制御機構の検討2019

    • Author(s)
      中脇充章、見目智紀、内田健太郎、名倉直重、田澤諒、井上玄、髙相晶士
    • Organizer
      第46回日本肩関節学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腱板断裂患者の肩峰下滑液包においてNGFの発現が上昇する2019

    • Author(s)
      田澤諒、見目智紀、内田健太郎、名倉直重、中脇充章、井上玄、髙相晶士
    • Organizer
      第46回日本肩関節学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Differential mRNA expression of COX-2 and proinflammatory mediators in patients with rotator cuff tears and osteoarthritis of the hip2019

    • Author(s)
      Kenmoku T, Uchida K, Fukushima K, Takahira N, Nagura N, Nakawaki M, Tazawa R, Muneshige K, Takaso M
    • Organizer
      20th EFORT congress Lisbon
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腱板断裂後TNF-alphaは持続的に発現しNGFの発現を誘導する2018

    • Author(s)
      名倉直重、見目智紀、内田健太郎、中脇充章、田澤 諒、大貫裕子、井上 玄、高相晶士
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] ラット腱板断裂モデルの腱修復過程におけるマクロファージサブタイプの経時的変化2018

    • Author(s)
      名倉直重、見目智紀、内田健太郎、中脇充章、田澤諒、大貫裕子、井上 玄、高相晶士
    • Organizer
      第33回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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