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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.

Research Project

Project/Area Number 16K20081
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Anesthesiology
Research InstitutionNiigata University

Principal Investigator

Ohashi Nobuko  新潟大学, 医歯学総合病院, 助教 (70706712)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
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)
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
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.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2017 2016

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] 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.2017

    • Author(s)
      Ohashi N, Uta D, Sasaki M, Ohashi M, Kamiya Y, Kohno T
    • Journal Title

      Anesthesiology.

      Volume: 127 Issue: 2 Pages: 355-371

    • DOI

      10.1097/aln.0000000000001700

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] アセトアミノフェンは炎症性疼痛に対しても脊髄レベルでより強い鎮痛効果を発揮する‐脊髄後角ニューロンにおけるin vivoおよびin vitroパッチクランプ記録を用いた検討‐2017

    • Author(s)
      大橋宣子、歌大介、佐々木美佳、大橋正幸、紙谷義孝、河野達郎
    • Organizer
      日本麻酔科学会 第64回学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Underlying mechanisms of acetaminophen in the spinal dorsal horn neurons2016

    • Author(s)
      Nobuko Ohashi, Daisuke Uta, Mika Sasaki, Yoshinori Kamiya, Tatsuro Kohno
    • Organizer
      Society for Neuroscience 46th Annual Meeting
    • Place of Presentation
      San Diego(アメリカ合衆国)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] アセトアミノフェンの鎮痛機序2016

    • Author(s)
      大橋宣子
    • Organizer
      日本臨床麻酔学会 第36回大会 シンポジウム 神経炎症と組織炎症の観点から考える痛みのメカニズム
    • Place of Presentation
      高知市文化プラザかるぽーと(高知県高知市)
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] アセトアミノフェンの脊髄後角ニューロンにおける鎮痛機序2016

    • Author(s)
      大橋宣子、佐々木美佳、河野達郎
    • Organizer
      日本麻酔科学会第63回学術集会
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-05-26
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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