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 Fiscal Year Final Research Report

• Project/Area Number: 16K20081
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Niigata 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
• 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

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.

Free Research Field

麻酔科学分野