How do antidepressants which inhibit norepinephrine and serotonin reuptake reduce pain?
These drugs work on the descending inhibitory pathways.
They increase K + influx and block Ca ++ influx at the second-order neuron in the dorsal horn.
It should be noted, however, that this mechanism of action depends on the type of 5-HT receptor since some subtypes are excitatory rather than inhibitory.