Effect of acetaminophen on central noradrenergic pain inhibition

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K16749
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Osaka City University
• Principal Investigator: Fujimoto Yohei 大阪市立大学, 大学院医学研究科, 講師 (90779430)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: アセトアミノフェン / 鎮痛 / 下降性抑制系 / ノルアドレナリン

Outline of Final Research Achievements

We evaluated the central noradrenergic involvement on anti-hyperalgesic effect of acetaminophen. We utilized in vivo microdialysis in locus ceruleus and spine with concurrent pain-related behavioral evaluation using rodent models of various phases of inflammatory pain. Acetaminophen related noradrenergic activation was observed only in the subacute phase pain model. The observed anti-hyperalgesic effect in the subacute phase model was attenuated by intrathecal alpha-2 antagonist yohimbine. The result of our study indicated that acetaminophen related phase-specific central noradrenergic activation was involved in its anti-hyperalgesic effect. This finding may reflect the involvement of acetaminophen’s action via central noradrenergic pain inhibitory system on the pain modulation process during pain chronification or the protective action against it.

Free Research Field

麻酔

Academic Significance and Societal Importance of the Research Achievements

アセトアミノフェンは世界で最も頻用される薬の一つであるにも関わらずその鎮痛作用の機序について全貌が解明されていなかった。本研究ではその鎮痛機序において新たな可能性を示すとともに、特に疼痛の慢性化に至る過程を念頭に置いた時間軸に注目した実験系において研究結果を示した。諸外国でオピオイドの乱用が社会問題化する中、非麻薬性鎮痛薬であるアセトアミノフェンが重要性を増している現状があり、本研究結果が今後アセトアミノフェンの使用戦略に影響を与える可能性がある。