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

Abstract

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.

New technologies to investigate the brain-gut axis

“…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 [78] . Taken together these findings strongly suggest that abnormalities in the brain-gut axis play a key role in our understanding of FGID, and future studies using the techniques described above will undoubtedly increase our understanding of these disorders.…”

Significant psychological morbidity occurs in irritable bowel syndrome: a case‐control study using a pharmacy reimbursement database

“…7 The antidepressant medicines amitriptyline and citalopram are both effective in IBS, independent of their effect on depression and anxiety. 8,9 Cognitive behavioural therapy has also been employed in the treatment of IBS, with mixed results. 10,11 Psychological distress severely impairs response to IBS treatment.…”

How to Perform and Interpret Functional Magnetic Resonance Imaging Studies in Functional Gastrointestinal Disorders

“…27 Several studies have attempted to identify the specific mechanisms of treatment 86 and neuroimaging biomarkers for further disorders. 87 The inhibition effect of pain-related brain activation in IBS patients by amitriptyline (tricyclic antidepressants) 20 identified the central mechanism of antidepressants in the reduction of rectal distention pain. The brain activity during acupuncture suggested the modulation of serotonin pathway at insula and the higher cortical regulation of affection as potential neural mechanisms of acupuncture treatment.…”