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Structure determination and physiological effect analysis of a novel brain-derived physiologically active substance that suppresses intractable neuropathic pain

Research Project

Project/Area Number 20K07768
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 51030:Pathophysiologic neuroscience-related
Research InstitutionKyoto Tachibana University

Principal Investigator

IKEDA Tetsuya  京都橘大学, 健康科学部, 教授 (20264369)

Co-Investigator(Kenkyū-buntansha) 井田 隆徳  宮崎大学, フロンティア科学総合研究センター, 准教授 (00381088)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsallodynia / APGWamide / 神経因性疼痛 / 神経障害性疼痛 / 慢性疼痛 / CCI / CCIモデルラット / 絞扼性神経損傷モデル / 絞扼性神経障害モデル / アロディニア / pain / 座骨神経圧迫モデル
Outline of Research at the Start

慢性痛の中でも神経因性疼痛は、難治性でいまだ有効な治療法がない。高齢化社会の進展に伴い、神経因性疼痛患者も増大しており効果的な治療薬の開発が喫緊の課題になっている。軟体動物の神経ペプチド(APGWamide)が神経因性疼痛モデルラットの疼痛を軽減することから、本研究では同族体を脊椎動物の脳神経系から単離精製し、その生理機能を明らかにすることを目的とした。特に、哺乳類から強力な神経因性疼痛抑制物質が得られれば、ヒトに対する効果も期待できる。その新規疼痛抑制物質を出発物質として、新たな神経因性疼痛治療薬の開発につなげていきたい。

Outline of Final Research Achievements

The purpose of this study is to isolate and purify a novel anti-allodynic substance from the chicken nervous system using allodynia of a neuropathic pain model rat as a bioassay system. Since APGWamide, a molluscan neuropeptide, exhibits analgesic effects on allodynia in rats, we considered the possibility that similar anti-allodynic peptides exist in vertebrates. As a result, we were able to (1) establish an assay system for a rat pain model, and (2) obtain two types of purified products from 1000 chicken brain tissues. Unfortunately, the absolute amount of the final purified product was small, and the structure could not be determined. In the process of developing the assay system, we also investigated the structure-activity relationship using analog peptides of APGWamide.

Academic Significance and Societal Importance of the Research Achievements

神経因性疼痛は難治性で有効な治療薬の開発が望まれている。神経因性疼痛モデルラットの行動実験をバイオアッセイに用いて新規生理活性物質を探索することは、本研究の最大の特徴であり、他に例を見ない独創的な手法である。今回2種類の新規疼痛抑制物質を単離できた。構造解析までは至らなかったが、新たな疼痛抑制物質を単離する方法の開発に貢献できたと考えている。さらに、軟体動物の神経ペプチドであるAPGWamideの神経因性疼痛に対する鎮痛効果の構造活性関係も解析し、N-末端のアミノ酸残基が活性の発現に重要な役割を果たしていることがわかった。この結果を基に新たな鎮痛薬の開発につながることが期待できる。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (4 results)

All 2023 2022 2021

All Presentation (4 results)

  • [Presentation] The anti-allodynic effect of peptide hormone, oxytocin, on the rat with chronic constriction injury to the sciatic nerve2023

    • Author(s)
      Ryo Okumura, Jun Kato and Tetsuya Ikeda
    • Organizer
      The 46th Annual Meeting of the Japan Neuroscience Society, Sendai
    • Related Report
      2023 Annual Research Report
  • [Presentation] Antiallodynic effect of APGWamide analogue peptides are subjected to the involvement of descending pain inhibitory system2023

    • Author(s)
      Jun Kato, Ryo Okumura and Tetsuya Ikeda
    • Organizer
      The 45th Annual Meeting, Japanese Society for Comparative, Physiology and Biochemistry, Osaka
    • Related Report
      2023 Annual Research Report
  • [Presentation] The effect of a peptide hormone, oxytocin, on a rat model of neuropathic pain2022

    • Author(s)
      Ryo Okumura, Jun Kato and Tetsuya Ikeda
    • Organizer
      44th Annual Meeting, Japanese Society for Comparative, Physiology and Biochemistry, Kochi
    • Related Report
      2022 Research-status Report
  • [Presentation] The effect of the analogue peptides of APGWamide on rat models of inflammatory and neuropathic pain2021

    • Author(s)
      Ryota Sawami, Ayumi Nakaya, Reina Fujimura, Futaba Nishikawa, Yuzuho Yoshii and *Tetsuya Iked
    • Organizer
      43rd Annual Meeting (online), Japanese Society for Comparative, Physiology and Biochemistry
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2025-01-30  

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