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神経栄養因子によるペインセンサーTRPA1の機能調節機構

Publicly Offered Research

Project AreaMolecular interaction and modal shift of cellular sensors
Project/Area Number 21026028
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionHyogo Medical University

Principal Investigator

野口 光一  兵庫医科大学, 医学部, 教授 (10212127)

Co-Investigator(Kenkyū-buntansha) 戴 毅  兵庫医療大学, 薬学部, 准教授 (20330441)
Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2010: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2009: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywords疼痛 / 後根神経節 / TRPA1 / シグナル伝達 / パッチクランプ
Research Abstract

免疫染色およびIn situハイブリダイゼション法による二重染色の結果より、NGFのレセプターであるTrkA、GDNF/ArteminのレセプターであるRetがTRPA1と高率に共存するデータが得られた。一方、GFRa1はTRPA1とほとんど共存していないが、GFRa2の約40%、GFRa3の約90%がTRPA1と共存することも判明した。形態学のデータはこれら神経栄養因子によってTRPA1が何らかの機能調節を受ける可能性が示唆された。結果として、ArtemirRet/GFRによるTRPA1の生理機能調節機構をホールセルパッチクランプ法にて調べたところ、Artemin100ng/mlの短時間投与はAITCによるTRPA1電流を減少させ、TRPA1の機能を促進ではなくむしろ抑制することが明らかとなった。ところが、カプサイシンによるTRPV1電流はArteminによっては変化を示さなかった。カルシウムイメージング法においても、AITC投与によるカルシウム応答のArteminによる抑制的効果が確認された。さらに動物の行動実験において、足底へのAITC投与による疼痛行動がArteminの事前投与により抑制されることも明らかとなった。以上のデータは、短時間投与のArteminは、TRPA1チャネルの活動性を抑制することを示しており、全く新しいデータとして国際的一流雑誌に投稿し、現時点でRevision中である。

Report

(2 results)
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (28 results)

All 2011 2010 2009

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (21 results)

  • [Journal Article] Comparative study of voltage-gated sodium channel α -subunits in non-overlapping four neuronal populations in the rat dorsal root ganglion2011

    • Author(s)
      Fukuoka T., et.al.
    • Journal Title

      Neurosci.Res.

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leukotriene synthases and the receptors induced by peripheral nerve injury in the spinal cord contribute to the generation of neuropathic pain2010

    • Author(s)
      Okubo M., et.al.
    • Journal Title

      Glia

      Volume: 58 Pages: 599-610

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of transient receptor potential ankyrin 1(TRPA1) in the rat trigeminal sensory afferents and spinal dorsal horn2010

    • Author(s)
      Kim YS., et.al.
    • Journal Title

      J Comp Neurol

      Volume: 518 Pages: 687-98

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laminae-specific distribution of alpha-subunits of voltage-gated sodium channels in the adult rat spinal cord2010

    • Author(s)
      Fukuoka T., et.al.
    • Journal Title

      Neuroscience

      Volume: 169 Pages: 994-1006

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Leukotriene synthases and the receptors induced by peripheral nerve injury in the spinal cord contribute to the generation of neuropathic pain2010

    • Author(s)
      Okubo M, et.al.
    • Journal Title

      Glia 58

      Pages: 599-610

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of TRPA1 receptor in the rat trigeminal sensory afferents and spinal dorsal horn2010

    • Author(s)
      Yun Sook Kim., et.al.
    • Journal Title

      J.Comp.Neurol. 518

      Pages: 687-698

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats2009

    • Author(s)
      Kondo T., et.al.
    • Journal Title

      Gut 58

      Pages: 1342-1352

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] 痛みの分子形態学的研究2011

    • Author(s)
      野口光一
    • Organizer
      筋骨格系疼痛シンポジウム
    • Place of Presentation
      名古屋
    • Year and Date
      2011-03-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] Artemin suppresses AITC-induced current in cultured DRG neurons and TRPA1-mediated pain behaviors2010

    • Author(s)
      野口光一, 他3名
    • Organizer
      特定領域研究「細胞感覚」冬の班会議inお台場
    • Place of Presentation
      東京
    • Year and Date
      2010-12-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] 痛みの分子メカニズム2010

    • Author(s)
      野口光一
    • Organizer
      第37回日本マイクロサージャリー学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-11-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] 痛みの分子メカニズム-最近の知見-2010

    • Author(s)
      野口光一
    • Organizer
      第10回近畿神経変性疾患研究会
    • Place of Presentation
      大阪
    • Year and Date
      2010-11-12
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経障害性疼痛の分子メカニズム2010

    • Author(s)
      野口光一
    • Organizer
      第21回日本末梢神経学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Potentiation of alpha, beta methylene-ATP induced P2X3 currents in primary afferent by PAR-2 signal is unlikely to involve receptor phosphorylation2010

    • Author(s)
      Dai Y., et.al.
    • Organizer
      13th World Congress on Pain (IASP)
    • Place of Presentation
      Montreal
    • Year and Date
      2010-09-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] IL-18-mediated microglia/astrocyte interaction contributes to neuropathic pain2010

    • Author(s)
      Noguchi K.
    • Organizer
      13th World Congress on Pain (IASP)
    • Place of Presentation
      Montreal
    • Year and Date
      2010-08-31
    • Related Report
      2010 Annual Research Report
  • [Presentation] 炎症性疼痛の分子メカニズム2010

    • Author(s)
      野口光一
    • Organizer
      第20回大阪リウマチカンファレンス
    • Place of Presentation
      大阪
    • Year and Date
      2010-08-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Inhibition of TRPA1 channel activity by glial cell line-derived neurotrophic factor family member, artemin2010

    • Author(s)
      野口光一, 他3名
    • Organizer
      特定領域研究「細胞感覚」夏の班会議in札幌
    • Place of Presentation
      札幌
    • Year and Date
      2010-07-05
    • Related Report
      2010 Annual Research Report
  • [Presentation] 神経傷害性疼痛の分子メカニズム2010

    • Author(s)
      野口光一
    • Organizer
      第39回日本脊椎脊髄病学会教育研修講演
    • Place of Presentation
      高知
    • Year and Date
      2010-04-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Sensitization of the P2X3 ATP receptor in primary afferent by proteinase-Activated Receptor 22010

    • Author(s)
      野口光一
    • Organizer
      The Decades of Dubner Scientific Symposium
    • Place of Presentation
      Baltimore
    • Year and Date
      2010-03-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 脊髄後角における痛覚伝達の分子メカニズム2009

    • Author(s)
      野口光一
    • Organizer
      第19回神経科学の基礎と臨床
    • Place of Presentation
      大阪
    • Year and Date
      2009-12-19
    • Related Report
      2009 Annual Research Report
  • [Presentation] 痛みの分子メカニズム2009

    • Author(s)
      野口光一
    • Organizer
      第11回 Macnab Memorial Lecture
    • Place of Presentation
      郡山
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Transient expression of TNF alpha in the rat spinal cord following peripheral nerve iujury2009

    • Author(s)
      Kobayashi K., et.al.
    • Organizer
      The 39th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Interleukin-1β converting enzyme(ICE)upregulation in spinal glial cells contributes to tactile allodynia after nerve injury2009

    • Author(s)
      Miyoshi K., et.al.
    • Organizer
      The 39th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Platelet-activating factor biosynthesis in spinal cord contributes to neuropathic pain following peripheral nerve injury2009

    • Author(s)
      Okubo M., et.al.
    • Organizer
      The 39th Annual Meeting of the Society for Neuroscience
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-18
    • Related Report
      2009 Annual Research Report
  • [Presentation] 炎症性疼痛の分子メカニズム2009

    • Author(s)
      野口光一
    • Organizer
      第1回日本線維筋痛症学会
    • Place of Presentation
      大阪
    • Year and Date
      2009-10-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] 痛みの分子メカニズム2009

    • Author(s)
      野口光一
    • Organizer
      第31回日本疼痛学会
    • Place of Presentation
      名古屋
    • Year and Date
      2009-07-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] 神経栄養因子によるペインセンサーTRPA1の機能調節機構2009

    • Author(s)
      野口光一
    • Organizer
      特定領域研究「細胞感覚」平成21年度夏の班会議
    • Place of Presentation
      沖縄
    • Year and Date
      2009-06-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] 痛みの分子メカニズム2009

    • Author(s)
      野口光一
    • Organizer
      第85回聖マリアンナ大学難治研センター大学院セミナー
    • Place of Presentation
      東京
    • Year and Date
      2009-06-09
    • Related Report
      2009 Annual Research Report
  • [Presentation] 痛み-その発生機序と臨床的制御の意義-「炎症性疼痛の分子メカニズム」2009

    • Author(s)
      野口光一
    • Organizer
      第53回日本リウマチ学会総会
    • Place of Presentation
      東京
    • Year and Date
      2009-04-25
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2018-03-28  

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