What is the mechanism of action for tricyclic antidepressants and SNRIs as adjuvant analgesics?

The mechanism of action for tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) as adjuvant analgesics is centered around their ability to enhance pain inhibition by blocking the reuptake of serotonin (5-HT) and norepinephrine (NE). By preventing the reabsorption of these neurotransmitters in the synaptic cleft, these medications increase their availability, which can lead to enhanced modulation of pain pathways.

The presence of elevated serotonin and norepinephrine levels in the central nervous system is associated with increased analgesic effects, primarily through the descending pain pathways that inhibit pain signaling. This biological mechanism is particularly beneficial in the treatment of certain types of chronic pain that are not adequately addressed by traditional analgesics, such as neuropathic pain.

In contrast, the other options do not accurately describe the role of TCAs and SNRIs. For instance, increasing the re-uptake of serotonin would have the opposite effect of what is therapeutic, while acting on kappa receptors is more related to opioid mechanisms rather than that of tricyclics or SNRIs. Lastly, reducing neurotransmitter levels would not support a therapeutic mechanism aimed at alleviating pain; instead