Tramadol differs from other traditional opioid medications in that it doesn't just act as a μ-opioid agonist, but also affects monoamines by modulating the effects of neurotransmitters involved in the modulation of pain such as serotonin and norepinephrine which activate descending pain inhibitory pathways.13 Tramadol's effects on serotonin and norepinephrine mimic the effects of other SNRI antidepressants such as duloxetine and venlafaxine.