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Identification of itch mediators using clinical samples of dialysis patients and application to clinical treatment

Research Project

Project/Area Number 16K15337
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Pain science
Research InstitutionUniversity of Toyama

Principal Investigator

ANDOH Tsugunobu  富山大学, 大学院医学薬学研究部(薬学), 准教授 (50333498)

Research Collaborator MOMOSE Akishi  
MAKI Takahito  
LI Sikai  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords痒み / 慢性腎不全 / β2マイクログロブリン / ヒスタミン / ロイコトリエンB4 / トロンボキサンA2 / インターロイキン-31 / 起痒物質 / 透析
Outline of Final Research Achievements

The elucidation of the mechanism of itching in hemodialysis patients with chronic renal failure was investigated. β2 microglobulin (β2-MG) in the serum of dialysis patients was increased. In addition to the finding that β2-MG was an itch mediator, it was demonstrated that β2-MG elicited itching through direct activation of TRPV1-expressed primary afferents. We succeeded in developing a mouse model with a chronic renal failure-related itching, and found that β2-MG, IL-31, and arachidonic acid metabolites were involved in itching. Furthermore, in the skin of hemodialysis patients with chronic renal failure, it was also found that itch mediators, such as IL-31, were expressed in the epidermis. These results suggest that these itch mediators may be new therapeutic targets for chronic renal failure-related itching

Academic Significance and Societal Importance of the Research Achievements

慢性腎不全による透析患者は、皮膚の乾燥並びに非常に激しい痒み訴える。このことは、透析自体による生活の質の低下に加え、痒みによる苦痛並びに不眠症に悩まされる。従って、痒み抑制は、患者にとって非常に重要である。しかし、このような痒みは痒みの第一選択薬である抗ヒスタミン薬が無効である場合が多く、新規治療薬の開発や治療ターゲットの発見が重要である。本研究において、透析患者の臨床試料並びに新たに開発した病態動物モデルを用いて痒みの新規治療ターゲットとしてヒスタミン以外にβ2 microglobulin、IL-31及びアラキドン酸代謝物を見出したことは学術的にも社会的にも非常に意義のある成果を得た。

Report

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

    (14 results)

All 2019 2018 2017

All Journal Article (5 results) (of which Peer Reviewed: 5 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] β2-Microglobulin, interleukin-31, and arachidonic acid metabolites (leukotriene B4 and thromboxane A2) are involved in chronic renal failure-associated itch-associated responses in mice2019

    • Author(s)
      Li Sikai、Andoh Tsugunobu、Zhang Qun、Uta Daisuke、Kuraishi Yasushi
    • Journal Title

      European Journal of Pharmacology

      Volume: 847 Pages: 19-25

    • DOI

      10.1016/j.ejphar.2019.01.017

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of thromboxane A 2 in interleukin-31-induced itch-associated response in mice2018

    • Author(s)
      Andoh Tsugunobu、Li Sikai、Uta Daisuke
    • Journal Title

      Pharmacol. Rep.

      Volume: 70 Issue: 2 Pages: 251-257

    • DOI

      10.1016/j.pharep.2017.10.001

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Non-myelinated C-fibers, but not myelinated A-fibers, elongate into the epidermis in dry skin with itch2018

    • Author(s)
      Andoh Tsugunobu、Asakawa Yuta、Kuraishi Yasushi
    • Journal Title

      Neuroscience Letters

      Volume: 672 Pages: 84-89

    • DOI

      10.1016/j.neulet.2018.02.034

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Peripheral gabapentin regulates mosquito allergy-induced itch in mice2018

    • Author(s)
      Akiyama Tasuku、Andoh Tsugunobu、Ohtsuka Eiji、Nojima Hiroshi、Ouchi Hidekazu、Takahata Hiroki、Kuraishi Yasushi
    • Journal Title

      European Journal of Pharmacology

      Volume: 833 Pages: 44-49

    • DOI

      10.1016/j.ejphar.2018.05.037

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] β2-Microglobulin elicits itch-related responses in mice through the direct activation of primary afferent neurons expressing transient receptor potential vanilloid 12017

    • Author(s)
      Andoh Tsugunobu、Maki Takahito、Li Sikai、Uta Daisuke
    • Journal Title

      Eur J Pharmacol.

      Volume: 810 Pages: 134-140

    • DOI

      10.1016/j.ejphar.2017.07.007

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 「かゆみ(痒み)」のいろいろ2019

    • Author(s)
      安東嗣修
    • Organizer
      県民カレッジ連携講座 放送大学富山学習センター「冬のオープンセミナー」(
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 皮膚の痒み発症メカニズムについて2018

    • Author(s)
      安東嗣修
    • Organizer
      ルパフィン学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Characteristics of primary afferent nerve fibers elongated into the epidermis in dry skin with itch2018

    • Author(s)
      Tsugunobu Andoh, Yuta Asakawa, Yasushi Kuraishi
    • Organizer
      The 48th Annual Meeting of the Society for Neuroscience (Neuroscience2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Pharmacological and histochemical characterization of a mouse model of chronic renal failure-associated pruritus.2017

    • Author(s)
      Tsugunobu Andoh, Sikai Li, Takatoshi Maki, Daisuke Uta, Yasushi Kuraishi
    • Organizer
      9th World Congress on Itch.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Involvement of beta2-microglobulin and transient receptor potential vanilloid 1-expressed primary afferent neurons in uremic pruritus2017

    • Author(s)
      Tsugunobu Andoh, Takatoshi Maki, Sikai Li, Daisuke Uta
    • Organizer
      The 47th Annual Meeting of the Society for Neuroscience
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 痒みのメカニズム:動物モデルを用いた最新の痒み研究2017

    • Author(s)
      安東嗣修
    • Organizer
      第116回日本皮膚科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 新規痒み因子β2 マイクログロブリンの発見と痒み発生機序2017

    • Author(s)
      牧 俊人,李 嗣凱,歌 大介,安東嗣修
    • Organizer
      日本薬学会北陸支部第129回例会
    • Related Report
      2017 Research-status Report
  • [Presentation] シャンプーや台所洗剤等に含まれる界面活性剤によって起こる痒みの発生メカニズム―痒み研究最前線―2017

    • Author(s)
      安東嗣修
    • Organizer
      平成29年度富山大学サテライト講座
    • Related Report
      2017 Research-status Report
  • [Book] Visual Dermatology2017

    • Author(s)
      安東嗣修(分担)【責任編集:室田浩之】
    • Total Pages
      100
    • Publisher
      秀潤社
    • ISBN
      9784780903966
    • Related Report
      2017 Research-status Report

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

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