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Brain-Spinal Cord Plasticity Changes during the Establishment of Chronic Pain: Elucidation of the Role of Inhibitory Neural Circuits

Research Project

Project/Area Number 18K08811
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55050:Anesthesiology-related
Research InstitutionNiigata University

Principal Investigator

Miyuki Kurabe  新潟大学, 医歯学系, 助教 (30635579)

Co-Investigator(Kenkyū-buntansha) 佐々木 美佳  新潟大学, 医歯学系, 助教 (20774061)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords青斑核 / in vivoパッチクランプ / 化学遺伝学的手法 / 薬理遺伝学的手法 / 慢性痛 / 脊髄後角 / 可塑性変化 / in vivo patch clamp / 脊髄可塑性
Outline of Final Research Achievements

We hypothesized that not only hyperexcitability of excitatory neurotransmission but also hyperexcitability of inhibitory neuronal circuits may be involved in the synaptic plasticity changes that develop during the establishment of chronic pain. We aimed to elucidate the role of inhibitory circuits in spinal plasticity from the early stage of peripheral nerve injury to the establishment of chronic pain, focusing especially on the descending inhibitory system.
Using the DREADD system, we selectively activated neurons in locus coeruleus, one of the originating nuclei of the descending inhibitory system, and analyzed their effects on pain responses. In addition to the in vivo patch-clamp method, behavioral and immunohistological analyses were also performed to conduct an integrated study to elucidate the role of the descending inhibitory system in pain.

Academic Significance and Societal Importance of the Research Achievements

神経障害後からの経時的な脊髄後角抑制性シナプス電流の解析を初めて行った。その結果、神経障害後の経過とともに変化し、最終的に慢性痛時にはGABAあるいはGlycineの受容体の感受性変化により応答が減弱していることを示した。一方で、化学遺伝学的手法を用いて下降性抑制系の起始核の一つである青斑核NAニューロンを操作したところ急性痛に対してNAニューロンの活性化は鎮痛作用を示した。神経障害後からのシナプス可塑性変化が従来の慢性痛治療が難渋する理由の一つである可能性が示唆された。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A mechanism of re-sedation caused by remimazolam2021

    • Author(s)
      Yamamoto Tomohiro、Kurabe Miyuki、Kamiya Yoshinori
    • Journal Title

      Journal of Anesthesia

      Volume: 6 Issue: 3 Pages: 467-468

    • DOI

      10.1007/s00540-021-02930-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Re-sleeping after reversal of remimazolam by flumazenil2021

    • Author(s)
      Yamamoto Tomohiro、Kurabe Miyuki、Kamiya Yoshinori
    • Journal Title

      Journal of Anesthesia

      Volume: 35 Issue: 2 Pages: 322-322

    • DOI

      10.1007/s00540-021-02915-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serotonin Plays a Key Role in the Development of Opioid-Induced Hyperalgesia in Mice2021

    • Author(s)
      Sasaki Mika、Kamiya Yoshinori、Bamba Keiko、Onishi Takeshi、Matsuda Keiichiro、Kohno Tatsuro、Kurabe Miyuki、Furutani Kenta、Yanagimura Harue
    • Journal Title

      The Journal of Pain

      Volume: - Issue: 6 Pages: 715-729

    • DOI

      10.1016/j.jpain.2020.12.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Congenital Tracheal Aplasia Without Prenatal Diagnosis Masked by Maternal Obesity and Gestational Diabetes2020

    • Author(s)
      Yamamoto Tomohiro、Kurabe Miyuki、Matsumoto Kensuke、Sugai Shunya、Baba Hiroshi
    • Journal Title

      A & A Practice

      Volume: 14 Issue: 6 Pages: e01200-e01200

    • DOI

      10.1213/xaa.0000000000001200

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] 慢性痛への移行にはアストロサイト-ニューロン相互作用による脊髄後角のneuronal lossが関与する2020

    • Author(s)
      倉部美起
    • Organizer
      日本麻酔科学会第67回学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] "Changes in spinal dorsal horn neuron characteristics from the early stage of peripheral nerve injury to chronic pain transition2019

    • Author(s)
      Miyuki Kurabe, Mika Sasaki, Hiroshi Baba
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
  • [Presentation] Alterations in Receptive Fields and Response Properties of Spinal Dorsal Horn Neurons in Rats after Peripheral Nerve Injury: An in vivo patch-clamp recording2018

    • Author(s)
      Miyuki Kurabe
    • Organizer
      the anesthesiology annual meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-01-27  

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