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Elucidation of the Mechanism of Combination Effects of Neuropathic Pain Therapeutics: Toward Enhancing the Effects of Gabapentinoids

Research Project

Project/Area Number 18K16437
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Hiroki Tadanao  群馬大学, 医学部附属病院, 助教 (90736753)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords神経障害性疼痛 / ガバペンチン / アミトリプチリン / 神経障害性痛 / ガバペンチノイド / 青斑核
Outline of Final Research Achievements

Neuropathic pain is treated with neuropathic pain medications such as gabapentinoids and opioids such as morphine, but the analgesic effect is limited and side effects are common. Initially, we investigated whether the analgesic effect of neuropathic pain medications could be enhanced by their concomitant use, but this did not produce any results. Therefore, experiments were conducted to elucidate the mechanism by which the analgesic effect of morphine is attenuated in neuropathic pain. In this study, we demonstrated that functional changes in the spinal dorsal horn interneuron GABAA receptors, which are part of the descending pain modulation system, contribute to the attenuated analgesic effect.

Academic Significance and Societal Importance of the Research Achievements

神経障害性疼痛に対する新規薬剤の開発が限定的な中、現状使用できる薬剤の効果を高める、副作用の出現を減らすことは臨床的意義が非常に大きい。本研究によってオピオイドの鎮痛作用減弱メカニズムの一つを明らかにできた。将来的に鎮痛効果を高める併用薬剤等を検討することで、神経障害性疼痛や治療薬の副作用の軽減に寄与できると考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2022 2020 2019 2018

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Spinal γ-Aminobutyric Acid Interneuron Plasticity Is Involved in the Reduced Analgesic Effects of Morphine on Neuropathic Pain2022

    • Author(s)
      Hiroki Tadanao、Suto Takashi、Ohta Jo、Saito Shigeru、Obata Hideaki
    • Journal Title

      The Journal of Pain

      Volume: 23 Issue: 4 Pages: 547-557

    • DOI

      10.1016/j.jpain.2021.10.002

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of endogenous analgesia leads to delayed recovery from incisional pain in a rat model of chronic neuropathic pain2020

    • Author(s)
      Ohta J, Suto T, Kato D, Hiroki T, Obata H, Saito
    • Journal Title

      Brain Res

      Volume: 1727 Pages: 146568-146568

    • DOI

      10.1016/j.brainres.2019.146568

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of four documents describing adrenaline purification, and the work of three important scientists, Keizo Uenaka, Nagai Nagayoshi and Jokichi Takamine2020

    • Author(s)
      Mieda Rie、Aso Chizu、Hiroki Tadanao、Kanamoto Masafumi、Suto Takashi、Tobe Masaru、Saito Shigeru
    • Journal Title

      Journal of Anesthesia History

      Volume: 6 Issue: 2 Pages: 42-48

    • DOI

      10.1016/j.janh.2020.04.001

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 脊髄GABA作動性介在ニューロンの可塑的変化によりモルヒネの神経障害性疼痛への鎮痛効果が減弱する.2020

    • Author(s)
      廣木忠直 須藤貴史 太田淨 齋藤繁 小幡英章
    • Organizer
      日本麻酔科学会第67回学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] The plasticity of spinal γ-aminobutyric acid interneurons reduces analgesic effects of morphine in neuropathic pain.2019

    • Author(s)
      Tadanao Hiroki, Takashi Suto, Jo Ohta, Shigeru Saito, Hideaki Obata.
    • Organizer
      Neuroscience 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 神経障害性痛ではモルヒネの鎮痛作用が減弱する-セロトニン作動性下行性痛み調節系の可塑性変化についての検討-2018

    • Author(s)
      廣木忠直
    • Organizer
      日本麻酔科学会第65回学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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