[citation needed] The SSRI antidepressant paroxetine did not display a gender difference in antinociceptive effects in mice.
[8] Voltage-gated ion channels are implicated in pain sensation and transmission signaling mechanisms within both peripheral nociceptors and the spinal cord.
[9] Activation of the μ-opioid receptor (MOR) and norepinephrine reuptake inhibition (NRI) are mechanisms of acute and chronic pain.
OPRM1 knockout mice were used to determine the relative contribution of MOR activation to tapentadol and morphine induced analgesia.
This indicated that the antinociceptive effect of tapentadol is based on a combined mechanism of action involving both MOR and NRI.