Imipramine decreases oesophageal pain perception in human male volunteers

Department of Medicine, Suite 501, Pepper Pavilion, Allegheny University Hospitals, Graduate, One Graduate Plaza, 1800 Lombard Street, Philadelphia, Pennsylvania 19146, USA

Correspondence to: Dr D O Castell.

Accepted for publication 19 January 1998

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 effect, 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 effect 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 different between placebo and imipramine. Balloon inflation volume at pain threshold was higher on imipramine (p=0.015). Median intraballoon pressures were not different at pain threshold for placebo and imipramine. Oesophageal wall compliance was not affected 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 effect.
(GUT 1998;:807-813)

Keywords: antidepressants;  imipramine;  visceral hyperalgesia;  oesophageal balloon;  distension;  functional bowel syndromes