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Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome
  1. V Morgan1,
  2. D Pickens1,
  3. S Gautam2,
  4. R Kessler1,
  5. H Mertz3
  1. 1Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA
  2. 2Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA
  3. 3Department of Medicine, and Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, Tennessee, USA
  1. Correspondence to:
    Dr H Mertz
    Vanderbilt University, St Thomas Hospital, 4230 Harding Rd Ste 309 West, Nashville, TN 37205, USA;


Background and aims: Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress.

Methods: Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music.

Results: Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress.

Conclusions: The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.

  • IBS, irritable bowel syndrome
  • CNS, central nervous system
  • fMRI, functional magnetic resonance imaging
  • ACC, anterior cingulate cortex
  • TCAs, tricyclic antidepressants
  • SSRIs, selective serotonin reuptake inhibitors
  • PET, positron emission tomography
  • amitriptyline
  • rectal pain
  • anterior cingulate cortex
  • irritable bowel syndrome
  • tricyclic antidepressants
  • functional magnetic resonance imaging

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  • This study was funded by NIH grant R21 DK57047.

  • Conflict of interest: None declared.

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