Differential effects of amitriptyline on perception of somatic and visceral stimulation in healthy humans

Abstract

Tricyclic antidepressants treat chronic pain both in patients with somatic illness and with functional bowel disorders. We compared the effects of amitriptyline on perception of cutaneous and gastrointestinal stimulation to assess differential analgesic effects of tricyclics on somatic and visceral pain. Cutaneous electrical stimulation and rectal and esophageal distension were performed before and after 21 days of double-blind 50 mg amitriptyline vs. placebo in healthy volunteers. Amitriptyline increased currents that elicited cutaneous threshold, moderate discomfort, and moderate pain compared with basal ( P < 0.05), whereas placebo had no effect. Amitriptyline had no effect on perception of rectal and esophageal distension and did not alter luminal compliance; thus the lack of effect on perception is not due to altered visceral elastic wall properties. In conclusion, amitriptyline reduces perception of cutaneous stimulation but does not alter visceral perception or compliance. This investigation demonstrates differential effects of tricyclics on somatic and visceral afferent function in healthy humans and provides insight into mechanisms of action in chronic pain both from somatic disease and from functional bowel disorders.

Pathophysiology and treatment of functional dyspepsia

“…However, studies of the effects of antidepressants on visceral sensitivity are rare, and the existing data on visceral sensitivity are controversial. 82,83 In a small study, amitriptyline was found to improve symptoms of functional dyspepsia without an effect on gastric sensitivity. 84 Fedotozine, a peripherally acting kappa opioid receptor agonist, influences visceral sensitivity, 85,86 and it has been shown to increase discomfort thresholds to gastric distension in healthy volunteers.…”

Desvenlafaxine succinate ameliorates visceral hypersensitivity but delays solid gastric emptying in rats

“…There is increasing evidence that antidepressants are useful for the treatment of FD, in particular for the treatment of visceral hypersensitivity. Some studies have demonstrated that TCAs and SSRIs have neuromodulatory and analgesic properties (5,11,17). However, the analgesic mechanisms of antidepressants remain unclear.…”

Translational pain research: Evaluating analgesic effect in experimental visceral pain models

“…In terms of its mechanism of action, amitriptyline inhibits serotonin and noradrenaline re-uptake almost equally. A pain model that involved esophageal and rectal distension was not sensitive to amitriptyline [7] . This study applied a rather uncontrolled stimulation paradigm in which there was a risk for bias in stimulus intensity [9] .…”

“…An experimental pain model activates different modalities and can be used to investigate the mechanism of action of different analgesics in detail. In combination with pharmacokinetic studies and objective assessment such as electroencephalography, new information re-sants and anticonvulsants) [3][4][5][6][7] .…”