Amitriptyline modifies the visceral hypersensitivity response to acute stress in the irritable bowel syndrome

Aliment Pharmacol Ther. 2009 Mar 1;29(5):552-60. doi: 10.1111/j.1365-2036.2008.03918.x. Epub 2008 Dec 12.


Background: Acute physical stress causes alteration in gut autonomic function and visceral hypersensitivity in patients with irritable bowel syndrome (IBS). We have developed a model to measure this stress response.

Aim: To assess whether treatment with a drug effective in treating IBS (amitriptyline) alters the response to acute stress in IBS patients.

Methods: Nineteen patients with IBS were given amitriptyline 25-50 mg. Patients underwent physical stress (cold pressor) test at baseline and after 3 months of treatment. Physiological parameters measured were: stress perception; systemic autonomic tone [heart rate (HR) and blood pressure (BP)]; gut specific autonomic innervation [rectal mucosal blood flow (RMBF)] and visceral sensitivity (rectal electrosensitivity).

Results: Fourteen of 19 (74%) patients improved symptomatically after 3 months of amitriptyline. Acute stress induced increased perception of stress and systemic autonomic tone and reduced RMBF in symptomatic responders and nonresponders (P > 0.05 for all). All nonresponders but only 3 of 14 responders continued to exhibit stress-induced reduced pain threshold at 3 months (change from baseline -31% vs. +2%, P < 0.03 respectively).

Conclusion: In this open study, amitriptyline appears to decrease stress-induced electrical hypersensitivity; this effect is independent of autonomic tone. The gut response to acute stress deserves further study as a model to study drug efficacy in IBS.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Amitriptyline / therapeutic use*
  • Analgesics, Non-Narcotic / therapeutic use*
  • Female
  • Humans
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / physiopathology
  • Irritable Bowel Syndrome / drug therapy*
  • Irritable Bowel Syndrome / physiopathology
  • Male
  • Middle Aged
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Rectum / drug effects*
  • Rectum / physiopathology
  • Statistics as Topic
  • Viscera / drug effects*
  • Viscera / physiopathology
  • Young Adult


  • Analgesics, Non-Narcotic
  • Amitriptyline