Elucidation of the underlying mechanism of acetaminophen in the brain and spinal cord

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15566
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Niigata University
• Principal Investigator: Tatsuro Kohno 新潟大学, 医歯学系, 准教授 (00313536)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: アセトアミノフェン / 脊髄後角

Outline of Final Research Achievements

The widely used analgesic acetaminophen is metabolized to N-acylphenolamine (AM404), which induces analgesia by acting directly on TRPV1 or CB1 receptors in the brain. Although these receptors are also abundant in the spinal cord, no previous studies have reported analgesic effects of acetaminophen or AM404 mediated by the spinal cord dorsal horn. We used in vivo and in vitro whole-cell patch-clamp recordings of dorsal horn neurons to assess excitatory synaptic transmission. Intravenous acetaminophen decreased peripheral pinch-induced excitatory responses in the dorsal horn. Direct application of AM404 decreased glutamate release from C primary afferent terminals. We determined that these phenomena were mediated by TRPV1, but not CB1 receptors. Our results suggest that the acetaminophen metabolite AM404 induces analgesia directly via TRPV1 receptors expressed on C-fibers in the spinal dorsal horn and suggest a mechanism by which acetaminophen induces analgesia.

Free Research Field

麻酔科学