| Project/Area Number |
17K09036
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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 |
Pain science
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| Research Institution | Kumamoto University |
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Principal Investigator |
YAMAMOTO TATSUO 熊本大学, 大学院生命科学研究部(医), 教授 (20200818)
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| Co-Investigator(Kenkyū-buntansha) |
生田 義浩 熊本大学, 病院, 准教授 (90264308)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | AM404 / CB-1受容体 / FAAH / TRPV1 / CB1受容体 / 青斑核 / 中脳水道周辺灰白質 / 吻側延髄腹内側部 / マイクロダイアリシス / 下行性疼痛抑制系 / アセトアミノフェン / 痛み / 炎症 / 鎮痛機序 |
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| Outline of Final Research Achievements |
The mechanism of acetaminophen to produce an analgesic effect is still unclear. AM404, a metabolite of acetaminophen, is a promising candidate to produce an analgesic effect. Acetaminophen was deacetylated at a liver to p-aminophenol. P-aminophenol is conjugated with arachidonic acid by FAAH in the CNS. AM404 act as an CB1 receptor and TRPV1 agonist. In the present study, we injected AM404 intracerebroventricularly (ICV) and examined the analgesic effect using rat formalin test model. We also microinjected into periaqueductal gray (PAG), rostral ventromedial medulla (RVM) and locus coeruleus (LC).
ICV injected AM404 produced an analgesic effect dose-dependently at a dose between 300 and 3000 g. 500 g of AM404 microinjected into PAG, RVM and LC also produced an analgesic effect. These data suggested that an analgesic effect of acetaminophen was, at least partly, mediated by the action of AM404 at PAG, RVM and LC.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の研究にて、アセトアミノフェンの鎮痛メカニズムの一つに下行性疼痛抑制系の活性化が関与していることが示された。今後の鎮痛薬開発に当たり、CB1受容体・TRPV1と下行性疼痛抑制系との関連に注目する必要があると考えられた。
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