| Project/Area Number |
18K16475
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Niigata University |
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Principal Investigator |
SASAKI MIKA 新潟大学, 医歯学系, 助教 (20774061)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | セロトニン / アストロサイト / モルヒネ / オピオイド誘発性痛覚過敏 / 脊髄後角 |
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| Outline of Final Research Achievements |
In this study, a model of opioid-induced hyperalgesia (OIH) with repeated intraperitoneal administration of morphine was developed to elucidate the pathogenesis of paradoxical opioid-induced hyperalgesia, and the involvement of serotonin was investigated. Morphine-induced OIH was inhibited by the 5-HT3 receptor antagonist ondansetron (OND) and the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA). On the other hand, there was an increase in pain-related protein phosphorylated ERK and astrocyte activation during the onset of OIH, but no inhibitory effect of OND or PCPA administration.
These results suggest that serotonin in the dorsal horn of the spinal cord is largely involved in OIH and that astrocyte activation may be secondary.
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| Academic Significance and Societal Importance of the Research Achievements |
麻薬性鎮痛薬（オピオイド）は，周術期疼痛管理やがん性疼痛の緩和治療に必須の鎮痛薬である一方，オピオイドの比較的大量投与や長期使用により，鎮痛効果とは逆の作用である逆説的な痛覚過敏（Opioid-Induced Hyperalgesia : OIH）を生じることが知られており，オピオイドの使用に対する臨床上の解決すべき問題となっている．本研究から，OIHにはセロトニンが深く関与していることが明らかになり，セロトニン及びその受容体がOHIの治療・予防標的となりうることが示された．
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