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The assessment of molecular/cellular pathophysiology and the development of neuroimaging for spinal cord-related pain

Research Project

Project/Area Number 16K10817
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionUniversity of Fukui

Principal Investigator

Nakajima Hideaki  福井大学, 学術研究院医学系部門, 講師 (10397276)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords脊髄障害性疼痛 / 神経障害性疼痛 / ニューロイメージング / PK1195 / PET / マイクログリア / マクロファージ / 脊髄損傷 / 脊髄症 / PK11195 / PET/MRI / ミクログリア / 圧迫性脊髄症 / 遺伝子解析
Outline of Final Research Achievements

We performed experiments on animal model and clinical study to aim to make visible the microglia activation by neuroimaging. PK11195 is antagonist of peripheral benzodiazepine receptor (PBR) that migrate to cell membrane depending on the microglia activation in response to spinal cord dysfunction.
In the animal model, PBR positive cells were colocalized with CD11b and iba-1. Most of PBR-positive cells were not merged with GFP-positive cells. In autoradiography, accumulation of PK11195 was identified after injury. In the clinical study, no uptake was seen in the healthy volunteer and the uptake was seen only in patients within one year after the neuropathic pain onset. Our results suggest that PBR is mainly located in activated microglia, and [11C]-PK11195 PET/MRI imaging is available to investigate whether microglial activation is evident in for the patients with neuropathic pain.

Academic Significance and Societal Importance of the Research Achievements

末梢神経損傷による神経障害性疼痛については、その病因メカニズムが研究されている一方で、脊髄実質の損傷による脊髄障害性疼痛発現の病態については未だ不明な点が多い。本研究では、GFP マウスの骨髄細胞移植のキメラマウスとを用いることで、脊髄由来あるいは骨髄由来のmicroglia/macrophgeを区別してそれぞれの役割を明らかにする。また11C-(R)PK11195-PET は活性型ミクログリアの可視化と報告されており、脳-脊髄の活性化ミクログリアの動態を捉えることができれば、この病態解明や治療効果判定など臨床的な面からも多大の貢献を成すものと考えられる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (12 results)

All 2018 2017 2016

All Journal Article (3 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Comparison of Mesenchymal Stromal Cells Isolated from Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury.2018

    • Author(s)
      Takahashi A, Nakajima H, Uchida K, Takeura N, Honjoh K, Watanabe S, Kitade M, Kokubo Y, Johnson WEB, Matsumine A.
    • Journal Title

      Cell Transplantation

      Volume: 27 Issue: 7 Pages: 39-47

    • DOI

      10.1177/0963689718780309

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 迫性頚髄症モデル(twyマウス)を用いた脊髄障害性疼痛に関する基礎的研究2016

    • Author(s)
      竹浦直人, 中嶋秀明, 髙橋 藍, 他
    • Journal Title

      中部整災誌

      Volume: 59 Pages: 675-676

    • Related Report
      2016 Research-status Report
  • [Journal Article] 脊髄障害性疼痛;特集「日常診療と慢性疼痛の管理」2016

    • Author(s)
      中嶋秀明
    • Journal Title

      成人病と生活習慣病

      Volume: 46 Pages: 835-838

    • Related Report
      2016 Research-status Report
  • [Presentation] PK11195 PET imagingを用いた脊髄内活性化ミクログリア可視化の試み2018

    • Author(s)
      中嶋秀明、北出誠、渡邉修司、本定和也、山本悠介、松峯昭彦
    • Organizer
      第47回日本脊椎脊髄病学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Clinical assessment using PK11195 PET/MRI imaging for neuropathic pain in the patients with cervical spinal cord injury and compressive myelopathy.2018

    • Author(s)
      Nakajima H, Kitade M, Watanabe S, Honjoh K, Yamamoto Y, Matsumine A.
    • Organizer
      Cervical Spine Research Society Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ラット脊髄損傷におけるmicrogliaの[11C]-PK11195によるPETイメージング2017

    • Author(s)
      北出誠、中嶋秀明、渡邉修司、他.
    • Organizer
      第32回日本整形外科基礎学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Clinical assessment using MRI/18F-FDG PET fusion imaging for patients with cervical compressive myelopathy2017

    • Author(s)
      Nakajima H, Honjoh K, Watanabe S, et al.
    • Organizer
      Cervical Spine Research Society Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脊骨髄間葉系幹細胞移植は疼痛関連シグナルおよび炎症細胞浸潤抑制を介して脊髄損傷後疼痛抑制に寄与する2016

    • Author(s)
      中嶋秀明, 渡邉修司, 本定和也, 他
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 慢性圧迫脊髄におけるMRI輝度変化と血液脊髄関門の透過性変化2016

    • Author(s)
      竹浦直人, 中嶋秀明, 髙橋 藍, 他
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] CCL21欠損マウス脊髄損傷モデルにおける疼痛関連評価および損傷部・腰膨大部のmicroglia/ macrophage phenotypeと炎症性サイトカインの評価2016

    • Author(s)
      本定和也, 中嶋秀明, 髙橋 藍, 他
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] ラット脊髄損傷におけるmicrogliaの[11C]-PK11195によるPETイメージング2016

    • Author(s)
      北出 誠, 中嶋秀明, 渡邉修司, 他
    • Organizer
      第31回日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 脊髄再生と疼痛2016

    • Author(s)
      中嶋秀明
    • Organizer
      第38回日本疼痛学会
    • Place of Presentation
      北海道立道民活動センター(北海道札幌市)
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2020-03-30  

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