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The pathomechanism of chronic low back pain through CGRP signaling

Research Project

Project/Area Number 17K16700
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKitasato University

Principal Investigator

Miyagi Masayuki  北里大学, 医学部, 講師 (90627556)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords椎間板性腰痛 / カルシトニン遺伝子関連ペプチド / 神経成長因子 / マクロファージ / 起源 / 炎症性サイトカイン
Outline of Final Research Achievements

CGRP and NGF could contribute to pain in several musculoskeletal disorders. We examined M1 and M2 macrophage markers, CGRP and NGF and cytokine expression in IVD-derived cells from control and IVD-injured mice for 28 days following injury. Ngf mRNA expression was increased 1 day after injury in injured compared to control mice, and persisted for up to 28 days. Flow cytometric analysis demonstrated that the proportion of F4/80+CD11b+ cells was significantly increased from 1 day after injury for up to 28 days.TNF-α and TGF-β stimulated Ngf mRNA and NGF protein expression in IVD cells. Our results suggest that TNF-α and TGF-β may stimulate NGF production under inflammatory and non-inflammatory conditions following IVD injury. As TNF-α and TGF-β are produced by M1 and M2 macrophages, further investigations are needed to reveal the role of macrophages in NGF expression following IVD injury. Our results may aid in developing treatments for IVD-related LBP pathology.

Academic Significance and Societal Importance of the Research Achievements

腰痛の生涯罹患率は85%と報告され、超高齢者社会を迎えた我が国における腰痛患者は2,800万人にものぼる。本邦の厚生労働省の報告では腰痛は男性1位、女性2位にランクされる重大な国民愁訴である。多大な医療費がこの腰痛疼痛治療に費やされているのが現状であり、腰痛による経済損失は年間7,000億円と推定されている。本研究成果に基づいた更なる腰痛機序の解明と治療法の開発は社会・医療経済的にも重要な意義を持つ。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018 2017

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (7 results)

  • [Journal Article] Investigation of resident and recruited macrophages following disc injury in mice.2020

    • Author(s)
      Kawakubo A, Uchida K, Miyagi M, Nakawaki M, Satoh M, Sekiguchi H, Yokozeki Y, Inoue G, Takaso M.
    • Journal Title

      J Orthop Res

      Volume: - Issue: 8 Pages: 1703-1709

    • DOI

      10.1002/jor.24590

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sequential CCL2 Expression Profile After Disc Injury in Mice.2020

    • Author(s)
      Nakawaki M, Uchida K, Miyagi M, Inoue G, Kawakubo A, Kuroda A, Satoh M, Takaso M
    • Journal Title

      J Orthop Res

      Volume: 38 Issue: 4 Pages: 895-901

    • DOI

      10.1002/jor.24522

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes in NGF expression and macrophage phenotype following intervertebral disc injury in mice2019

    • Author(s)
      Nakawaki M, Uchida K, Miyagi M, Inoue G, Kawakubo A, Sato M, Takaso M
    • Journal Title

      J Orthop Res

      Volume: 印刷中 Issue: 8 Pages: 1798-1804

    • DOI

      10.1002/jor.24308

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Macrophage-derived inflammatory cytokines regulate growth factors and pain-related molecules in mice with intervertebral disc injury.2017

    • Author(s)
      Maiygi M, Uchida K, Takano S, Fujimaki H, Aikawa J, Sekiguchi H, Nagura N, Ohtroi S, Inoue G, Takaso M.
    • Journal Title

      J Orthop Res

      Volume: - Issue: 8 Pages: 2274-2279

    • DOI

      10.1002/jor.23888

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 椎間板内在性マクロファージの分化能の検討2019

    • Author(s)
      川久保歩、内田健太郎、宮城正行、中脇充章、井上玄、齋藤亘、関口裕之、高相晶士
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] GFP骨髄キメラマウスを用いた椎間板障害後に増加するマクロファージの起源解析2019

    • Author(s)
      5.川久保歩、内田健太郎、宮城正行、中脇充章、井上玄、齋藤亘、関口裕之、高相晶士
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト椎間板組織におけるTGF-βを介したNGF発現制御2019

    • Author(s)
      城正行、内田健太郎、中脇充章、川久保歩、井上玄、中澤俊之、井村貴之、齋藤亘、白澤栄樹、関口裕之、高相晶士
    • Organizer
      第34回日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] マウス椎間板傷害モデルにおいてTNF-aはCCL2/CCR2を介して椎間板内にマクロファージを動員する.2018

    • Author(s)
      中脇充章、内田健太郎、宮城正行、中澤俊之、井村貴之、齋藤 亘、白澤栄樹、川久保 歩、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] マウス椎間板損傷モデルにおいて nerve growth factorは急性期と慢性期では異なる機構で制御されている2018

    • Author(s)
      中脇充章、内田健太郎、宮城正行、中澤俊之、井村貴之、齋藤亘、白澤栄樹、川久保歩、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] ヒト椎間板への過重負荷が疼痛関連物質の発現上昇を誘導する2018

    • Author(s)
      宮城正行、中脇充章、内田健太郎、高野昇太郎、井上 玄、中澤俊之、井村貴之、齋藤 亘、白澤 栄樹、大貫裕子、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] 椎間板の痛み2017

    • Author(s)
      宮城正行、井上玄、内田健太郎、石川哲大、鴨田博人、佐久間詳浩、西能健、川上守、高橋和久、大鳥精司、高相晶士
    • Organizer
      日本リウマチ学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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