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Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome
Open accessAbstract
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.
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“Modulating activity of the brain regions responsible for visceral pain using various therapies has been shown to improve IBS symptomatology.[36][37][38]”
From British Society of Gastroenterology guidelines on the management of irritable bowel syndrome (2021) · cites this paper as [37]
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“Furthermore, treatments targeting the CNS, such as antidepressants and psychological interventions, can reduce intestinal sensation/sensitivity and improve GI symptoms in patients with IBS (21, 111, 150, 165).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [111]
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The functional gastrointestinal disorders and the Rome III process
Drossman, D. A. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.03.008 · Cited by 2,416
Guidelines on the irritable bowel syndrome: mechanisms and practical management
Spiller, R., Aziz, Q., Creed, F., Emmanuel, A., Houghton, L., Hungin, P., Jones, R., Kumar, D., Rubin, G., Trudgill, N., et al. (2007) · Gut · doi:10.1136/gut.2007.119446 · Cited by 818
Role of the Prefrontal Cortex in Pain Processing
Ong, W., Stohler, C. S., & Herr, D. R. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1130-9 · Cited by 824
Chronic Pain and Mental Health Disorders
Hooten, W. M. (2016) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2016.04.029 · Cited by 571
British Society of Gastroenterology guidelines on the management of irritable bowel syndrome
Vasant, D. H., Paine, P. A., Black, C. J., Houghton, L. A., Everitt, H. A., Corsetti, M., Agrawal, A., Aziz, I., Farmer, A. D., Eugenicos, M. P., et al. (2021) · Gut · doi:10.1136/gutjnl-2021-324598 · Cited by 592
Metadata
- Authors
- Morgan, V
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- Morgan, V
- ORCID
- Morgan, V
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2005-05-01
- Volume
- 54
- Issue
- 5
- Pages
- 601-607
- ISSN
- 0017-5749 (ISSN-L)
- PMC
- PMC1774484
- OpenAlex
- W2168058358
- Cited by
- 269
- References
- 57
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 12 · 2023: 6 · 2022: 6 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 9 · 2015: 15 · 2014: 20 · 2013: 17 · 2012: 9
- FWCI
- 14.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institutes of Health (5r21dk057047-02)
- National Institute of Diabetes and Digestive and Kidney Diseases (R21 DK57047)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Infant Health and Development
- Keywords
- irritable bowel syndrome, amitriptyline, tricyclic antidepressants, anterior cingulate cortex, rectal pain, brain activation, stress, insula, prefrontal cortex, posterior parietal cortex, intestinal hypersensitivity
- MeSH terms
- Adult, Amitriptyline, Antidepressive Agents, Tricyclic, Brain, Brain Mapping, Dilatation, Double-Blind Method, Female, Gyrus Cinguli, Humans, Hyperalgesia, Magnetic Resonance Imaging, Middle Aged, Pain Measurement, Physical Stimulation, Psychiatric Status Rating Scales, Rectum, Stress, Psychological, Cross-Over Studies, Analgesics, Non-Narcotic, Irritable Bowel Syndrome
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