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Studies on central mechanisms of acute and chronic itch and its network in the spinal cord

Research Project

Project/Area Number 16H05233
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pain science
Research InstitutionOsaka Medical College (2018)
Kansai Medical University (2016-2017)

Principal Investigator

Ito Seiji  大阪医科大学, その他部局等, 客員教授 (80201325)

Co-Investigator(Kenkyū-buntansha) 松村 伸治  関西医科大学, 医学部, 准教授 (70276393)
西田 和彦  関西医科大学, 医学部, 助教 (80448026)
井上 明俊  関西医科大学, 医学部, 助教 (50709152)
Pham Minh・Vuong  関西医科大学, 医学部, 研究員 (50828853)
Research Collaborator UCHIDA Hitoshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2016: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywords痒みの動物モデル / クロロキン / セロトニン / ガストリン放出ペプチド / NMDA受容体 / c-fosの発現 / 脊髄と延髄 / 遺伝子改変マウス / 痒み / 慢性掻痒 / 伝達経路 / 脳部位 / c-fos / 発現解析 / ジニトロフルオロベンゼン / ビタミンD / 神経障害性掻痒 / ビタミンD3アナログ / 末梢神経再生モデル / 痒みの伝達経路 / 起痒物質 / 三叉神経脊髄路核 / 蛍光タンパク / in situハイブリダイゼーション / 慢性掻痒モデル / 痒みの神経機構 / 脊髄後角 / 多光子励起顕微鏡
Outline of Final Research Achievements

Itch is defined as unpleasant sensation that evokes the desire to scratch, but chronic itch is a tormenting symptom in patients with atopic dermatitis and hemodialysis. In normal skin, mechanical stimuli such as scratch and bite relieve itch and morphine, a strong analgesic, induces itch. Thus itch and pain are intimately related and may share transduction pathways in the peripheral and central nervous systems. However, transduction mechanisms of itch remain to be known.
In the present study, to address this, we prepared mouse models of acute and chronic itch and demonstrated the mechanisms and pathways common to itch and pain in the central nervous system.

Academic Significance and Societal Importance of the Research Achievements

これまで、我々はNMDA型グルタミン酸受容体の1つGluN2Bサブユニットの活性化が慢性疼痛の維持に関与することを明らかにしてきた。最近、ガストリン放出ペプチド(GRP)が痒みの神経伝達物質であることがわかり、痒みの研究が脚光を浴びている。
本研究で痒みの情報伝達にもGluN2Bサブユニットの活性化が重要であること、その活性化はGRP経路より上流で働くことを初めて明らかにした。さらに、痒みが知覚される脳への伝達経路は痛みと共通する部位があることを明らかにした。本研究成果は学術的な意義だけでなく、痒みの発生、維持機構を理解し、痒みをコントロールし、治療するための重要な知見となる。

Report

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

    (33 results)

All 2018 2017 2016 Other

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Presentation (18 results) (of which Int'l Joint Research: 9 results,  Invited: 2 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Distribution of Caskin1 protein and phenotypic characterization of its knockout mice using a comprehensive behavioral test battery2018

    • Author(s)
      Katano Tayo、Takao Keizo、Abe Manabu、Yamazaki Maya、Watanabe Masahiko、Miyakawa Tsuyoshi、Sakimura Kenji、Ito Seiji
    • Journal Title

      Molecular Brain

      Volume: 11 Issue: 1 Pages: 63-63

    • DOI

      10.1186/s13041-018-0407-2

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a novel photoaffinity probe for labeling nocistatin receptor.2018

    • Author(s)
      Harada M, Minami T, Ito S, Okuda-Ashitaka E.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: - Issue: 2 Pages: 514-519

    • DOI

      10.1016/j.bbrc.2018.05.028

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two isoforms of cyclic GMP-dependent kinase-I exhibit distinct expression patterns in the adult mouse dorsal root ganglion.2018

    • Author(s)
      Uchida Hitoshi、Matsumura Shinji、Katano Tayo、Watanabe Masahiko、Schlossmann Jens、Ito Seiji
    • Journal Title

      Molecular Pain

      Volume: 14 Pages: 1-11

    • DOI

      10.1177/1744806918796409

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impaired peripheral nerve regeneration in type-2 diabetic mouse model.2018

    • Author(s)
      Pham M. V., Nguyen H. T., Katano, T., Matsumura, S., Aaito, S., Yamada A., Furue, H. and Ito, S.
    • Journal Title

      European Journal of Neuroscience

      Volume: 47 Issue: 2 Pages: 126-139

    • DOI

      10.1111/ejn.13771

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RNA editing enzyme ADAR2 is a mediator of neuropathic pain after peripheral nerve injury.2017

    • Author(s)
      Uchida H, Matsumura S, Okada S, Suzuki T, Minami T and Ito S
    • Journal Title

      FASEB Journal

      Volume: 印刷中 Issue: 5 Pages: 1847-1855

    • DOI

      10.1096/fj.201600950r

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Na+/K+-ATPase coupled to endothelin receptor type B stimulates peripheral nerve regeneration via lactate signaling.2017

    • Author(s)
      Nguyen H. T., Katano, T., Matsumura, S., Funatsu, N., Pham, M. V., Fujisawa, JI. and Ito, S.
    • Journal Title

      European Journal of Neuroscience

      Volume: 46 Issue: 5 Pages: 2096-2107

    • DOI

      10.1111/ejn.13647

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Developmental origin of long-range neurons in the superficial dorsal spinal cord.2017

    • Author(s)
      Nishida, K., and Ito, S.
    • Journal Title

      European Journal of Neuroscience

      Volume: 46 Issue: 10 Pages: 2608-2619

    • DOI

      10.1111/ejn.13736

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conserved role of Ovo in germline development in mouse and Drosophila.2017

    • Author(s)
      Hayashi, M., Shinozuka, Y., Shigenobu, S., Sato, M., Sugimoto, M., Ito, S., Abe, K., Kobayashi, S.
    • Journal Title

      Scientific Report

      Volume: 6 Issue: 1 Pages: 40056-40056

    • DOI

      10.1038/srep40056

    • NAID

      120007135169

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phosphorylation of NMDA receptor GluN2B subunit at Tyr1472 is important for trigeminal processing of itch.2016

    • Author(s)
      Inoue A, Uchida H, Nakazawa T, Yamamoto T, Ito S.
    • Journal Title

      Eur J Neurosci.

      Volume: 44 Issue: 7 Pages: 2474-2482

    • DOI

      10.1111/ejn.13337

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microscopic visualization of testosterone in mouse testis by use of imaging mass spectrometry.2016

    • Author(s)
      Shimma, S., Kumada, H-O., Taniguchi, H., Konno, A., Yao, I., Furuta, K., Matsuda, T. and Ito, S.
    • Journal Title

      Analytical and bioanalytical chemistry

      Volume: 408 Issue: 27 Pages: 7607-7615

    • DOI

      10.1007/s00216-016-9594-9

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia via c-Jun N-terminal kinase and monocyte chemoattractant protein-1.2016

    • Author(s)
      Kawabata K, Nishimura I, Fujiwara T, Terauchi S, Minami T, Ito S, Okuda-Ashitaka E.
    • Journal Title

      Eur. J. Neurosci.

      Volume: 印刷中 Issue: 11 Pages: 1499-1508

    • DOI

      10.1111/ejn.13247

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Involvement of NIPSNAP1, a neuropeptide nocistatin-interacting protein, in inflammatory pain.2016

    • Author(s)
      Okamoto K, Ohashi M, Ohno K, Takeuchi A, Matsuoka E, Fujisato K, Minami T, Ito S, Okuda-Ashitaka E.
    • Journal Title

      Mol. Pain

      Volume: 12 Pages: 1-11

    • DOI

      10.1177/1744806916637699

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Involvement of Brain-Enriched Guanylate Kinase-Associated Protein (BEGAIN) in Chronic Pain after Peripheral Nerve Injury.2016

    • Author(s)
      Katano T, Fukuda M, Furue H, Yamazaki M, Abe M, Watanabe M, Nishida K, Yao I, Yamada A, Hata Y, Okumura N, Nakazawa T, Yamamoto T, Sakimura K, Takao T, Ito S.
    • Journal Title

      eNeuro.

      Volume: 3 Issue: 5 Pages: 0110-16

    • DOI

      10.1523/eneuro.0110-16.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] CASK-interacting protein 1 (Caskin1)の中枢神経系における機能的特徴の解析2018

    • Author(s)
      片野 泰代、高雄 啓三、阿部 学、山崎 真弥、渡辺 雅彦、宮川 剛、崎村 建司、伊藤 誠二
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Protein distribution and functional characterization of CASK-interacting protein 1 (Caskin1) in mice.2018

    • Author(s)
      Katano Tayo、Takao Keizo、Abe Manabu、Yamazaki Maya、Watanabe Masahiko、Miyakawa Tsuyoshi、Sakimura Kenji、Ito Seiji
    • Organizer
      Neuroscience 2018, 48th annual meeting of the Society for Neuroscience
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Na+/K+-ATPase coupled to ETBR promotes peripheral nerve regeneration via lactate signaling.2017

    • Author(s)
      Ito, S., Nguyen H.T., Katano, T., Matsumura, S., Funatsu, N. and Pham, M.V.
    • Organizer
      47th annual meeting of the Society for Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impaired peripheral nerve regeneration in type 2 diabetic mouse model.2017

    • Author(s)
      Pham, M.V., Nguyen H.T., Katano, T., Matsumura, S. and Ito, S.
    • Organizer
      47th annual meeting of the Society for Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Search of BEGAIN binding protein in the brain.2017

    • Author(s)
      Katano, T. and Ito, S.
    • Organizer
      47th annual meeting of the Society for Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of two nocistatin-binding proteins by using a novel photoaffinity probe.2017

    • Author(s)
      Harada, M., Minami, T., Ito, S. and Okuda-Ashitaka, E.
    • Organizer
      47th annual meeting of the Society for Neuroscience
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Identification of novel neuropathic pain-related proteins.2017

    • Author(s)
      Katano, T., Fukuda, M., Yamazaki, M., Abe, M., Watanabe, M., Yao, I., Okumura, N., Nakazawa, T. Yamamoto, T., Sakimura, K., Takao, T. and Ito, S.
    • Organizer
      BRI The 8th International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 痛みの研究の最新の知見2017

    • Author(s)
      伊藤誠二
    • Organizer
      学術講演会 医学の進歩シリーズ 平成29年度第1回
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 神経細胞特異的に蛍光タンパクを発現するマウスを用いた坐骨神経切断─再生モデルの確立と神経再生メカニズムの解析2017

    • Author(s)
      伊藤誠二、Nguyen Huu Tu、片野泰代、松村伸治、Pham Minh Vuong
    • Organizer
      日本麻酔科学会第64回学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 脊髄後角における神経障害性疼痛関連分子BEGAINの同定2017

    • Author(s)
      片野泰代、福田正史、山崎真弥、阿部学、渡辺雅彦、矢尾育子、奥村宣明、中澤敬信、山本雅、崎村建司、高尾敏文、伊藤誠二
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脊髄後角長距離投射ニューロンの発生2017

    • Author(s)
      西田和彦、伊藤誠二
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 神経障害性および炎症性疼痛モデルにおけるRNA編集異常2017

    • Author(s)
      内田仁司、松村伸治、崎村建司、伊藤誠二
    • Organizer
      第68回日本薬理学会北部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 痒みの神経伝達においてNMDA受容体GluN2BサブユニットのTyr1472のリン酸化は重要である2017

    • Author(s)
      井上明俊、中澤敬信、伊藤誠二
    • Organizer
      第110回近畿生理学談話会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 発生および慢性疼痛下の一次知覚神経におけるRNA編集の変動2017

    • Author(s)
      内田仁司、松村伸治、崎村建司、伊藤誠二
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Involvement of Na+/K+-ATPase in peripheral nerve regeneration via lactate signaling in sciatic nerve transection-regeneration model.2016

    • Author(s)
      Nguyen H.T., Katano, T., Matsumura, S., Pham, M.V. and Ito, S.
    • Organizer
      The 46th annual meeting of the Society for Neuroscience
    • Place of Presentation
      サンディエゴ(アメリカ合衆国)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nociceptin/Orphanin FQ-induced allodynia via c-Jun N-terminal kinase and monocyte chemoattractant protein-1 in the spinal cord.2016

    • Author(s)
      Okuda-Ashitaka, E., Kawabata, K., Nishimura, I., Fujiwara, T. Terauchi, S., Minami, T. and Ito, S.
    • Organizer
      16th World Congress on Pain
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study on the effect of diabetic neuropathy on peripheral nerve regeneration in mouse model.2016

    • Author(s)
      Pham, M.V., Nguyen H.T., Katano, T., Matsumura, S. and Ito, S.
    • Organizer
      16th World Congress on Pain
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 海馬におけるマウスBEGAINの生化学的解析2016

    • Author(s)
      片野泰代、渡辺雅彦、崎村建司、伊藤誠二
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター/東北大学川内北キャンパス(宮城県・仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Book] 痛覚のふしぎ 脳で感知する痛みのメカニズム2017

    • Author(s)
      伊藤誠二
    • Total Pages
      224
    • Publisher
      講談社
    • Related Report
      2016 Annual Research Report
  • [Remarks] 関西医科大学医化学講座

    • URL

      http://www3.kmu.ac.jp/medchem/index.html

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report

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

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