Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome

Morgan, V; Pickens, D; Gautom, S; Kessler, R; Merlz, H
May 2005
Gut;May2005, Vol. 54 Issue 5, p601
Academic Journal
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 LBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for 185. The aim of this study was to determine if low dose amitriplyline reduces ACC activation during painful rectal distension in lBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriplyline, and to determine if reductions in cerebral activation are greater during mental stress. Methods: Nineteen women with painful lBS were randomised to amitriplyline 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 amitriplyline 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. Amitriplyline 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 lBS.


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