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Mechanism of morphine-induced pain

Research Project

Project/Area Number 18K08831
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Matsuda Mitsumasa  東海大学, 医学部, 講師 (10384918)

Co-Investigator(Kenkyū-buntansha) 吉川 正信  東海大学, 医学部, 准教授 (90276791)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
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モルヒネ / 脊髄 / Dセリン / シアロルフィン / 唾液腺 / 疼痛 / 鎮痛 / オピオイド受容体 / Dアミノ酸 / NMDA受容体 / D体セリン / D-セリン / 鎮痛耐性 / Dセリン
Outline of Final Research Achievements

Microdialysis probes were inserted into the spinal cord under isoflurane anesthesia, and the amounts of D-serine and glutamic acid released by formalin stimulation were analyzed. The results showed that release of both D-serine and glutamic acid increased at both phase 1 and phase 2after formalin stimulation. The addition of morphine into dialyzate decreased D-serine and glutamate secretion. Sialorphine potentiates the analgesic effect induce by endogenous opioid peptides as an allosteric modulator for mu-opioid receptor. The gene and protein of D-amino acids, metabolism-related enzymes, and NMDA receptors in the salivary glands, the site of sialorphin biosynthesis, was found.

Academic Significance and Societal Importance of the Research Achievements

モルヒネを慢性あるいは高用量硬膜外投与するとアロディニアなどの疼痛が引き起こされる(モルヒネ誘導性疼痛)。脊髄後角ニューロンの過敏化に重要な役割を果たすNMDA受容体活性化にDセリン、シアロルフィン、オピオイドペプチド分解酵素が関与することが明らかに出来れば、これらを標的としたモルヒネ鎮痛効果の増強ならびにモルヒネの有害作用を軽減させる新たな治療薬を創出できる可能性がある。

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

    (1 results)

All 2022

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Free D-amino acids in salivary gland in rat2022

    • Author(s)
      Yoshikawa M, Kan T, Shirose K, Watanabe M, Matsuda M, Ito K, Kawaguchi M
    • Journal Title

      Biology

      Volume: 11 Issue: 3 Pages: 390-405

    • DOI

      10.3390/biology11030390

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access

URL: 

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

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