Imipramine decreases oesophageal pain perception in human male volunteers

Abstract

Background-Visceral hyperalgesia is a hallmark of functional gastrointestinal disorders. Antidepressants improve symptoms in these patients, although their mode of action is unclear. Antidepressant, anticholinergic, and analgesic mechanisms have been proposed. Aims-To investigate whether imipramine, which has a visceral analgesic eVect, increases pain thresholds to experimental visceral pain. Methods-Visceral perception for first sensation and pain was measured with intraoesophageal balloon distension in 15 male volunteers. The eVect of imipramine was studied in a double blind, placebo controlled, crossover study. Imipramine was given in ascending doses for 12 days (25 mg days 1-3, 50 mg days 4-6, 75 mg days 7-12), with oesophageal perception studied on day 13. Results-Inflation volumes and intraballoon pressures at first sensation were not diVerent between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not diVerent at pain threshold for placebo and imipramine. Oesophageal wall compliance was not aVected by imipramine. Conclusion-Increased pain thresholds on imipramine in this group of normal male volunteers in the absence of changes in oesophageal tone imply the presence of a visceral analgesic eVect. (Gut 1998;42:807-813)

Assessing efficacy of non‐opioid analgesics in experimental pain models in healthy volunteers: an updated review

“…Imipramine, ketamine [55,89] The table concludes and summarizes findings found above. Drugs in parentheses have different efficacy in different trials; the drug is then put in the category where evidence is strongest.…”

“…Deep pressure pain was decreased by imipramine, but the stimulus intensity needed to exceed the pain threshold for a significant effect [83,85]. Viscera: Non-nociceptive sensations and pain to distension of the oesophagus were investigated by Peghini et al, who found that only the painful sensations were affected [89].…”

“…The fact that imipramine works through many different analgesic mechanisms may also have contributed to the effects found in several experimental models. However, several studies show a pain-specific action of imipramine with a decrease of sensations at the pain detection threshold or of higher intensity [83,85,89].…”

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.…”

Oesophageal hypersensitivity is associated with features of psychiatric disorders and the irritable bowel syndrome

“…[32][33][34] We found it difficult to identify large numbers of PPI non-responders who were not already prescribed such medications. In a different study that did not include ambulatory pH monitoring or oesophageal sensation testing, we found that unselected PPI non-responders had more features of psychiatric disorders than PPI responders.…”