Acetaminophen Metabolite N-Acylphenolamine Induces Analgesia via Transient Receptor Potential Vanilloid 1 Receptors Expressed on the Primary Afferent Terminals of C-fibers in the Spinal Dorsal Horn.
| Project/Area Number |
16K20081
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Anesthesiology
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| Research Institution | Niigata University |
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Principal Investigator |
Ohashi Nobuko 新潟大学, 医歯学総合病院, 助教 (70706712)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | アセトアミノフェン / N-アシルフェノールアミン / パッチクランプ記録 / 脊髄後角 / TRPV1受容体 / AM404 / 薬理学 / 薬剤反応性 |
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| Outline of Final Research Achievements |
Acetaminophen is metabolized to N-acylphenolamine (AM404), which induces analgesia in the brain, but no previous studies have reported analgesic effects of acetaminophen mediated by the spinal cord dorsal horn.
First, we assessed in a rat using behavioral measures and revealed that systemic administration of acetaminophen and intrathecal injections of AM404 induces analgesia to thermal stimulation. Second, we used whole-cell patch-clamp recordings in the dorsal horn, and revealed that intravenous acetaminophen decreased peripheral pinch-induced excitatory responses, while direct application of acetaminophen did not reduce these responses. Direct application of AM404 decreased the amplitudes of monosynaptic EPSCs evoked by C-fibers stimulation. These phenomena were mediated by TRPV1, but not CB1, receptors.These results suggest that the acetaminophen metabolite AM404 induces analgesia directly via TRPV1 receptors expressed on central terminals of C-fibers in the spinal dorsal horn.
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Report
(3 results)
Research Products
(5 results)
