| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
|---|
| 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.
|
