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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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Citations
Cites
(1982) · Trends in Neurosciences · doi:10.1016/0166-2236(82)90076-5 · Cited by 9,150
Goodman and Gilman's the Pharmacological Basis of Therapeutics
Stigelman, W. H., & Pharm, D. (1986) · Military Medicine · doi:10.1093/milmed/151.1.386 · Cited by 6,796
Subgenual prefrontal cortex abnormalities in mood disorders
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997) · Nature · doi:10.1038/386824a0 · Cited by 2,693
The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis
Chrousos, G. P. (1992) · JAMA · doi:10.1001/jama.1992.03480090092034 · Cited by 2,689
Pain Affect Encoded in Human Anterior Cingulate But Not Somatosensory Cortex
Rainville, P., Duncan, G. H., Price, D. D., Carrier, B., & Bushnell, M. C. (1997) · Science · doi:10.1126/science.277.5328.968 · Cited by 2,629
Mayberg, H. S., Liotti, M., Brannan, S. K., McGinnis, S., Mahurin, R. K., Jerabek, P. A., Silva, J. A., Tekell, J. L., Martin, C. C., Lancaster, J. L., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.5.675 · Cited by 2,416
Lr, D., & Derogatis, L. R. (1983) · Medical Entomology and Zoology · Cited by 2,027
Primate anterior cingulate cortex: Where motor control, drive and cognition interface
Paus, T. (2001) · Nature Reviews Neuroscience · doi:10.1038/35077500 · Cited by 1,722
AGA technical review on irritable bowel syndrome.
Drossman, D. A., Camilleri, M., Mayer, E. A., & Whitehead, W. E. (2002) · Gastroenterology · doi:10.1053/gast.2002.37095 · Cited by 1,384
The cortical representation of pain
Treede, R.-D., Kenshalo, D. R., Gracely, R. H., & Jones, A. K. P. (1999) · Pain · doi:10.1016/s0304-3959(98)00184-5 · Cited by 1,077
Pain intensity processing within the human brain: a bilateral, distributed mechanism
Coghill, R. C., Sang, C. N., Maisog, J. M., & Iadarola, M. J. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.82.4.1934 · Cited by 1,077
Emotion, motivation, and anxiety: brain mechanisms and psychophysiology
Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00275-3 · Cited by 1,043
Altered rectal perception is a biological marker of patients with irritable bowel syndrome
Mertz, H., Naliboff, B. D., Munakata, J., Niazi, N., & Mayer, E. A. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)90267-8 · Cited by 976
Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome
Ritchie, J. (1973) · Gut · doi:10.1136/gut.14.2.125 · Cited by 832
Fear and the brain: where have we been, and where are we going?
LeDoux, J. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00282-0 · Cited by 782
Brain activity during transient sadness and happiness in healthy women
(1995) · American Journal of Psychiatry · doi:10.1176/ajp.152.3.341 · Cited by 737
Drugs and the treatment of psychiatric disorders
Baldessarini, R. J. (1996) · Medical Entomology and Zoology · Cited by 683
Whalen, P. J., Bush, G., McNally, R. J., Wilhelm, S., McInerney, S. C., Jenike, M. A., & Rauch, S. L. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00251-0 · Cited by 650
Drossman, D. A., Toner, B. B., Whitehead, W. E., Diamant, N. E., Dalton, C. B., Duncan, S., Emmott, S., Proffitt, V., Akman, D., Frusciante, K., et al. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00669-3 · Cited by 614
Tolerance for Rectosigmoid Distention in Irritable Bowel Syndrome
Whitehead, W. E., Holtkötter, B., Enck, P., Hoelzl, R., Holmes, K. D., Anthony, J. C., Shabsin, H. S., & Schuster, M. M. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90332-u · Cited by 592
Pain “relief” by frontal cingulumotomy
Foltz, E. L., & White, L. E. (1962) · Journal of Neurosurgery · doi:10.3171/jns.1962.19.2.0089 · Cited by 588
Mertz, H., Morgan, V. L., Tanner, G., Pickens, D. R., Price, R. R., Shyr, Y., & KESSLER, R. M. (2000) · Gastroenterology · doi:10.1016/s0016-5085(00)70170-3 · Cited by 585
Self-citationRegional cerebral activity in normal and pathological perception of visceral pain
Silverman, D. H. S., Munakata, J., Ennes, H. S., Mandelkern, M. A., Hoh, C. K., & Mayer, E. (1997) · Gastroenterology · doi:10.1016/s0016-5085(97)70220-8 · Cited by 546
Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis
Jackson, J. L., O’Malley, P. G., Tomkins, G., Balden, E., Santoro, J., & Kroenke, K. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(99)00299-5 · Cited by 466
Altered small bowel motility in irritable bowel syndrome is correlated with symptoms
Kellow, J. E., & Phillips, S. F. (1987) · Gastroenterology · doi:10.1016/0016-5085(87)90620-2 · Cited by 464
Paus, T., Koski, L. M., Caramanos, Z., & Westbury, C. F. (1998) · Neuroreport · doi:10.1097/00001756-199806220-00001 · Cited by 460
Svensson, T. H., & Usdin, T. B. (1978) · Science · doi:10.1126/science.213833 · Cited by 398
Vogt, B. A., Derbyshire, S. W. G., & Jones, A. K. P. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01608.x · Cited by 384
Chey, W. Y., Jin, H. O., Lee, M. H., Sun, S. W., & Lee, K. Y. (2001) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03804.x · Cited by 347
Brain-gut axis in health and disease
Aziz, Q., & Thompson, D. G. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70540-2 · Cited by 328
Naliboff, B. D., Derbyshire, S. W. G., Munakata, J., Berman, S. M., Mandelkern, M. A., Chang, L., & Mayer, E. A. (2001) · Psychosomatic Medicine · doi:10.1097/00006842-200105000-00006 · Cited by 325
Immunological changes in young and old adults during brief laboratory stress.
Naliboff, B. D., Benton, D. M., Solomon, G. F., Morley, J. E., Fahey, J. L., Bloom, E. T., Makinodan, T., & Gilmore, S. L. (1991) · Psychosomatic Medicine · doi:10.1097/00006842-199103000-00002 · Cited by 256
Aziz, Q., Andersson, J., Valind, S., Sundín, A., Hamdy, S., Jones, A. K. P., Foster, E., Långström, B., & Thompson, D. (1997) · Gastroenterology · doi:10.1016/s0016-5085(97)70079-9 · Cited by 255
Symptoms and visceral perception in severe functional and organic dyspepsia
Mertz, H., Fullerton, S. C., Naliboff, B. D., & Mayer, E. A. (1998) · Gut · doi:10.1136/gut.42.6.814 · Cited by 252
Sullivan, G. M., Coplan, J. D., KENT, J. M., & Gorman, J. M. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00246-2 · Cited by 250
Effect of anger on colon motor and myoelectric activity in irritable bowel syndrome
Welgan, P. R., Meshkinpour, H., & Beeler, M. (1988) · Gastroenterology · doi:10.1016/0016-5085(88)90006-6 · Cited by 224
Tricyclic antidepressants: Effects on the firing rate of brain noradrenergic neurons
Nybäck, H., Walters, J. R., Aghajanian, G. K., & Roth, R. H. (1975) · European Journal of Pharmacology · doi:10.1016/0014-2999(75)90297-6 · Cited by 222
Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex
Derbyshire, S. W. G., Vogt, B. A., & Jones, A. K. P. (1998) · Experimental Brain Research · doi:10.1007/s002210050254 · Cited by 218
Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress
Dickhaus, B., Mayer, E. A., Firooz, N., Stains, J., Conde, F. A., Olivas, T. I., Fass, R., Chang, L., Mayer, M., & Naliboff, B. D. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.07156.x · Cited by 204
Effects of desipramine on irritable bowel syndrome compared with atropine and placebo
Greenbaum, D. S., Mayle, J. E., Vanegeren, L. E., Jerome, J. A., Mayor, J., Greenbaum, R. B., Matson, R. W., Stein, G. E., Dean, H. A., Halvorsen, N. A., et al. (1987) · Digestive Diseases and Sciences · doi:10.1007/bf01297051 · Cited by 180
Gastric distention correlates with activation of multiple cortical and subcortical regions
Ladabaum, U., Minoshima, S., Hasler, W. L., Cross, D. J., Chey, W. D., & Owyang, C. (2001) · Gastroenterology · doi:10.1053/gast.2001.21201 · Cited by 157
The time course of noradrenergic pre- and postsynaptic activity during chronic desipramine treatment
Huang, Y. H., Maas, J. W., & Hu, G. H. (1980) · European Journal of Pharmacology · doi:10.1016/0014-2999(80)90058-8 · Cited by 132
Imipramine decreases oesophageal pain perception in human male volunteers
Peghini, P. L., Katz, P. O., & Castell, D. O. (1998) · Gut · doi:10.1136/gut.42.6.807 · Cited by 117
Antidepressants and chronic pain: Fig 1
McQuay, H. J., & Moore, R. A. (1997) · BMJ · doi:10.1136/bmj.314.7083.763 · Cited by 115
Gorelick, A. B., Koshy, S. S., Hooper, F. G., Bennett, T. C., Chey, W. D., & Hasler, W. L. (1998) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1998.275.3.g460 · Cited by 98
Craig, A., & Sorkin, L. S. (2011) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0000275.pub3 · Cited by 87
Evolution of Visceral Sensitivity in Patients with Irritable Bowel Syndrome
Poitras, P., Riberdy, M., Plourde, V., Boivin, M., & Verrier, P. (2002) · Digestive Diseases and Sciences · doi:10.1023/a:1014729125428 · Cited by 85
DEPRESSION AND ANXIETY DISORDERS
Brown, C. (2001) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/s0889-8545(05)70199-6 · Cited by 74
Pavcovich, L. A., Yang, M., Miselis, R. R., & Valentino, R. J. (1998) · Brain Research · doi:10.1016/s0006-8993(97)01178-5 · Cited by 72
Linnér, L., Arborelius, L., Nomikos, G. G., Bertilsson, L., & Svensson, T. H. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00126-2 · Cited by 52
Managing functional bowel disorders from the top down: lessons from a well-designed treatment trial
Clouse, R. E. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00808-4 · Cited by 43
Dazzi, L., Ladu, S., Spiga, F., Vacca, G., Rivano, A., Pira, L., & Biggio, G. (2001) · Synapse · doi:10.1002/syn.10024 · Cited by 40
Dazzi, L., Vacca, G., Ladu, S., Pisu, M. G., Serra, M., & Biggio, G. (2001) · Neuropharmacology · doi:10.1016/s0028-3908(01)00064-8 · Cited by 21
THE CONTRIBUTION OF FUNCTIONAL IMAGING TECHNIQUES TO OUR UNDERSTANDING OF RHEUMATIC PAIN
Jones, A. K. P. (1999) · Rheumatic Disease Clinics of North America · doi:10.1016/s0889-857x(05)70058-2 · Cited by 18
Pain management in the rheumatic diseases
Pisetsky, D. S., & Bradley, L. A. (1999) · Cited by 7
Increased activity of surviving locus ceruleus neurons in Alzheimer's disease
Moser (1999) · Pure Amsterdam UMC · doi:10.1002/1531-8249(199901)45:1
Flagged first, then by citations
1 of the 57 references couldn’t be matched to a known paper.
Research works printed but not linked: 8
- [9]9. Drossman DA, Toner BB, Whitehead WE, et al. Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology 2003;125:249-53.
- [21]21. Tolle TR, Kaufmann T, Siessmeier T, et al. Region-specific encoding of sensory and affective components of pain in the human brain: a positron emission tomography correlation analysis. Ann Neurol 1999;45:40-7.
- [22]22. Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in IBS and controls with painful and non-painful rectal distention. Gastroenterology 2000;118:842-8.
- [31]31. McQuay JH, Moore RA. Antidepressants and chronic pain. BMJ 1997;314:763-64.
- [37]37. Derbyshire S, Vogt B, Jones A. Pain and stroop interference tasks activate separate processing modules in anterior cingulate cortex. Exp Brain Res 1998;118:52-60.
- [47]47. LeDoux J. The neural circuits underlying anxiety and fear. Biol Psychiatry 1998;44:1229-38.
- [55]55. Welgan P, Meshkinpour H, Beeler M. Effect of anger on colon motor and myoelectric activityin irritable bowel syndrome. Gastroenterology 1988;94:1150-6.
- [56]56. Mertz H, Pickens D, Fass R, et al. Stress increases sensitivity to rectal distension in IBS but not control, associated with greater limbic system activation. Gastroenterology 2002;122:A311.
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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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