| Project/Area Number |
16K11754
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Nagasaki University |
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Principal Investigator |
KURATA Shinji 長崎大学, 病院(歯学系), 助教 (20325666)
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| Co-Investigator(Kenkyū-buntansha) |
上園 保仁 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20213340)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | オピオイド / オピオイド受容体 / 耐性 / 歯科麻酔学 |
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| Outline of Final Research Achievements |
To develop optimal perioperative analgesia, we investigated the effects of opioid receptor (OR) activity on opioid drugs and analgesics effect on the intracellular localization of μOR by visualization real-time analysis and Analysis of G-protein activity by the CellKey system.
(1) Remifentanil (RF) activates the G protein pathway of μORs, which is involved in analgesia, in a concentration-dependent manner. It also promotes the activity of the β-arrestin pathway, which is involved in side effects. (2) The combination of RF and S(+)ketamine have no effect on the G-protein activity of RF-activated μORs, but inhibits the activation of the β-arrestin pathway.
These results suggest that S(+) ketamine may be useful in preventing the development of RF-induced side effects such as acute tolerance formation.
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| Academic Significance and Societal Importance of the Research Achievements |
歯科・口腔外科領域では，持続的な鎮痛を行うことが難しく，手術の痛みや慢性痛で苦しむ患者も多い。鎮痛には医療用麻薬（オピオイド）が使用されているが，時に呼吸抑制や耐性形成（効きづらくなる）を発症しその対応に難しくなることがある。そこで副作用が少ないかつ効果的な鎮痛作用を併せ持つ，鎮痛方法の確立は重要である。本研究で得られた結果は，オピオイド製剤の特性を一部解明するとともに，呼吸抑制・耐性形成の副作用の問題を解決し，また適切な鎮痛方法の確立・新規鎮痛薬の開発に貢献できると考える。
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