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Identification of the role of noradrenaline system in the enhanced nociception-emotion link in chronic pain

Research Project

Project/Area Number 17K09042
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pain science
Research InstitutionJikei University School of Medicine

Principal Investigator

TAKAHASHI YUKARI  東京慈恵会医科大学, 医学部, 助教 (20613764)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords扁桃体 / 腕傍核 / シナプス可塑性 / モノアミン / 神経生理 / 神経科学
Outline of Final Research Achievements

Chronic pain is characterized by plastic changes in the brain networks. This study was undertaken to reveal the mechanism of pain chronification focusing on noradrenaline as an enhancer of plastic changes in pain network. We used a transgenic rat line, DBH-tTA-2A-Cre BAC Tg rat, to induce intrinsic noradrenaline release and analyze the effect of noradrenaline release on a pivotal synapse in pain pathway, the synapse between lateral parabrachial nucleus and central nucleus of the amygdala capsular part (LPB-CeC synapse). We injected AAV vector into a noradrenergic nucleus, nucleus solitary of tract, to express channelrhodopsin with cre-dependent manner. In acute brain slices, we induced intrinsic noradrenaline release by blue light and recorded light-evoked EPSCs in LPB-CeC synapse. We could observe slight synaptic modulation of noradrenaline and the effect of noradrenaline was enhanced by duloxietine, suggesting that the intrinsic noradrenaline release might be volume transmission.

Academic Significance and Societal Importance of the Research Achievements

ノルアドレナリン神経特異的Creリコンビナーゼ発現ラットと光遺伝学技術を組み合わせ、内因性ノルアドレナリン放出を誘発し、ノルアドレナリンのvolume transmissionを示唆するシナプス伝達修飾作用を捉えることに成功した。また、ペインマトリクス全体の痛みの慢性化過程での脳活動の可視化、および、それに対する経路特異的活動介入評価が可能な小動物MRIの実験系を得ることができ、痛みの慢性化におけるノルアドレナリン神経やその他の特異的な経路の役割解明の技術基盤を得た。これらの実験事実、実験手法に基づき今後研究を発展させることで、慢性痛治療における新たな治療標的の提示が期待される。

Report

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

    (22 results)

All 2020 2019 2018 2017 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 8 results) Presentation (10 results) (of which Int'l Joint Research: 4 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Right–side predominance of the central amygdala activation in trigeminal inflammatory pain model2020

    • Author(s)
      Takahashi Yukari、Miyazawa Yuta、Arimura Daigo、Sugimura Yae K、Kato Fusao
    • Journal Title

      PAIN RESEARCH

      Volume: 35 Issue: 1 Pages: 10-16

    • DOI

      10.11154/pain.35.10

    • NAID

      130007840287

    • ISSN
      0915-8588, 2187-4697
    • Year and Date
      2020-03-31
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alterations of voluntary behavior in the course of disease progress and pharmacotherapy in mice with collagen-induced arthritis2019

    • Author(s)
      Oto Yohsuke、Takahashi Yukari、Kurosaka Daitaro、Kato Fusao
    • Journal Title

      Arthritis Research & Therapy

      Volume: 21 Issue: 1 Pages: 284-284

    • DOI

      10.1186/s13075-019-2071-z

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Primary Role of the Amygdala in Spontaneous Inflammatory Pain- Associated Activation of Pain Networks - A Chemogenetic Manganese-Enhanced MRI Approach.2019

    • Author(s)
      Daigo Arimura, Kei Shinohara, Yukari Takahashi, Yae K Sugimura, Mariko Sugimoto, Tomokazu Tsurugizawa, Keishi Marumo, Fusao Kato
    • Journal Title

      Frontiers in neural circuits

      Volume: 13 Pages: 58-58

    • DOI

      10.3389/fncir.2019.00058

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ipsilateral-dominant control of limb movements in rodent posterior parietal cortex.2019

    • Author(s)
      1.Soma S, Yoshida J, Kato S, Takahashi Y, Nonomura S, Sugimura YK, Ríos A, Kawabata M, Kobayashi K, Kato F, Sakai Y, Isomura Y.
    • Journal Title

      J Neurosci.

      Volume: 39 Issue: 3 Pages: 485-502

    • DOI

      10.1523/jneurosci.1584-18.2018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predominant synaptic potentiation and activation in the right central amygdala are independent of bilateral parabrachial activation in the hemilateral trigeminal inflammatory pain model of rats.2018

    • Author(s)
      Miyazawa Y, Takahashi Y, Watabe AM, Kato F.
    • Journal Title

      Mol Pain.

      Volume: 14 Pages: 1-21

    • DOI

      10.1177/1744806918807102

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pain-associated neural plasticity in the parabrachial to central amygdala circuit -Pain changes the Brain, the Brain changes the Pain.2018

    • Author(s)
      Kato F, Sugimura YK, Takahashi Y.
    • Journal Title

      Adv Exp Med Biol.

      Volume: 1099 Pages: 157-166

    • DOI

      10.1007/978-981-13-1756-9_14

    • ISBN
      9789811317552, 9789811317569
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeted expression of step-function opsins in transgenic rats for optogenetic studies2018

    • Author(s)
      Igarashi Hiroyuki、Ikeda Keiko、Onimaru Hiroshi、Kaneko Ryosuke、Koizumi Kyo、Beppu Kaoru、Nishizawa Kayo、Takahashi Yukari、Kato Fusao、Matsui Ko、Kobayashi Kazuto、Yanagawa Yuchio、Muramatsu Shin-Ichi、Ishizuka Toru、Yawo Hiromu
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 5435-5435

    • DOI

      10.1038/s41598-018-23810-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Essential role of endogenous calcitonin gene-related peptide in pain-associated plasticity in the central amygdala2017

    • Author(s)
      Shinohara Kei、Watabe Ayako M.、Nagase Masashi、Okutsu Yuya、Takahashi Yukari、Kurihara Hiroki、Kato Fusao
    • Journal Title

      European Journal of Neuroscience

      Volume: 46 Issue: 6 Pages: 2149-2160

    • DOI

      10.1111/ejn.13662

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potentiation of NMDA receptor-mediated synaptic transmission at the parabrachial-central amygdala synapses by CGRP in mice2017

    • Author(s)
      Okutsu Yuya、Takahashi Yukari、Nagase Masashi、Shinohara Kei、Ikeda Ryo、Kato Fusao
    • Journal Title

      Molecular Pain

      Volume: 13 Pages: 1-11

    • DOI

      10.1177/1744806917709201

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【痛みに関する脳機能研究アーカイブズ】 扁桃体と痛み2017

    • Author(s)
      高橋由香里、加藤総夫
    • Journal Title

      ペインクリニック

      Volume: 38 Pages: 965-972

    • Related Report
      2017 Research-status Report
  • [Presentation] 三叉神経支配領域炎症性疼痛モデルにおける扁桃体疼痛制御機構2019

    • Author(s)
      高橋由香里
    • Organizer
      第41回日本疼痛学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Synaptic regulation by CGRP in the nociceptive amygdala2019

    • Author(s)
      高橋由香里
    • Organizer
      Neuro2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Neuropathic pain-associated plasticity in the nociceptive amygdala2019

    • Author(s)
      高橋由香里
    • Organizer
      第48回内藤コンファレンス
    • Related Report
      2019 Annual Research Report
  • [Presentation] Lateralized amygdala plasticity independent of bilateral parabrachial activity in inflammatory pain.2019

    • Author(s)
      Yukari Takahashi, Yuta Miyazawa, Yae K Sugimura, Fusao Kato.
    • Organizer
      The 9th Federation of the Asian and Oceanian Physiological Societies Congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The impact of the potentiated parabrachioamygdaloid synaptic transmissionon the central amygdala network signaling in the rats with neuropathic pain.2018

    • Author(s)
      Yukari Takahashi, Takeru Onozato, Tsuyoshi Tokita, Yae K Sugimura, Fusao Kato.
    • Organizer
      The 11th FENS Forum of Neuroscience
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optogeneticallyactivated monosynaptic transmission from the central amygdalato the periaqueductal gray in rats with inflammatory pain.2018

    • Author(s)
      Masoumeh Ghaemi-Jandabi, Zahra Ghasemi, Yukari Takahashi, Yae K Sugimura, Fusao Kato.
    • Organizer
      The 11th FENS Forum of Neuroscience
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 侵害受容扁桃体における神経ペプチドCGRPの役割.2018

    • Author(s)
      高橋由香里,加藤総夫.
    • Organizer
      平成30年度生理学研究所研究会「情動の神経回路機構とその破綻」
    • Related Report
      2018 Research-status Report
  • [Presentation] Effect of neuropathic pain on the optogenetically activated feedforward inhibition.2018

    • Author(s)
      Yukari Takahashi, Takeru Onozato, Yae K Sugimura, Fusao Kato.
    • Organizer
      Neuroscience 2018
    • Related Report
      2018 Research-status Report
  • [Presentation] The active role of the amygdala in the expression of the allodynia.2017

    • Author(s)
      Yukari Takahashi.
    • Organizer
      1st Pain and cortex summer meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 辺縁系~脳幹機能コネクトミクスのためのCreリコンビナーゼ発現ラットを用いたシナプス伝達解析.2017

    • Author(s)
      高橋由香里, 加藤総夫.
    • Organizer
      第45回自律神経生理研究会
    • Related Report
      2017 Research-status Report
  • [Book] Annual Review 神経 20192019

    • Author(s)
      加藤 総夫, 高橋由香里, 杉村 弥恵.
    • Total Pages
      7
    • Publisher
      中外医学社
    • ISBN
      9784498328303
    • Related Report
      2019 Annual Research Report
  • [Remarks] Jikei Neuroscience 東京慈恵会医科大学 総合医科学研究センター 神経科学研究部

    • URL

      http://www.jikei-neuroscience.com/website/publications/index.html

    • Related Report
      2019 Annual Research Report 2018 Research-status Report 2017 Research-status Report

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

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