Mechanism of morphine-induced pain

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08831
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Tokai 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
• 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

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.

Free Research Field

麻酔科学

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。