The analgesic activity of dothiepin (an antidepressant interacting with serotonin receptors) was studied (double-blind) in humans. A significant increase in nociceptive flexion reflex threshold and subjective pain threshold was observed after a 14-day dothiepin treatment. The effects of dothiepin on diffuse noxious inhibitory controls were also investigated using the cold-pressor test as conditioning stimuli. After dothiepin a reduced inhibition of nociceptive flexion reflex during the cold-pressor test and a significant facilitation immediately after the cold-pressor test were observed, while the subjective pain perception was normally inhibited. Our data suggest a serotonergic modulation of diffuse noxious inhibitory controls in humans.
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