Gastroenterology

Gastroenterology

Volume 131, Issue 2, August 2006, Pages 352-365
Gastroenterology

Clinical–alimentary tract
Longitudinal Change in Perceptual and Brain Activation Response to Visceral Stimuli in Irritable Bowel Syndrome Patients

https://doi.org/10.1053/j.gastro.2006.05.014Get rights and content

Background & Aims: Symptom-related fears and associated hypervigilance toward visceral stimuli may play a role in central pain amplification and irritable bowel syndrome (IBS) pathophysiology. Repeated stimulus exposure leads to decreased salience of threat and reduction of hypervigilance. We sought to evaluate hypervigilance in IBS visceral hypersensitivity and associated brain activity. Methods: Twenty IBS patients (14 female; moderate to severe symptoms) and 14 healthy controls participated in symptom and rectal distention assessments 6 times over 12 months. In a subset of 12 IBS patients, H215O-positron emission tomography images were obtained during baseline, rectal distentions, and anticipation of an aversive distention during the first and last session. Statistical parametric mapping (SPM99) was used to identify areas and networks activated during each session as well as those with differential activation across the 2 sessions. Results: Perceptual ratings of the rectal inflations normalized over 12 months, whereas IBS symptom severity did not. There were no sex-related differences in these response patterns. Stable activation of the central pain matrix was observed over 12 months, and activity in limbic, paralimbic, and pontine regions decreased. During the anticipation condition, there were significant decreases in amygdala, dorsal anterior cingulate cortex, and dorsal brainstem activation at 12 months. Covariance analysis supported the hypothesis of changes in an arousal network including limbic, pontine, and cortical areas underlying the decreased perception seen over the multiple stimulations. Conclusions: In IBS patients, repeated exposure to experimental aversive visceral stimuli results in the habituation of visceral perception and central arousal, despite stable activation of networks processing visceral pain and its anticipation.

Section snippets

Participants

Twenty IBS patients (6 male, 14 female; average age, 39.6 years; range, 23–55 years), recruited by advertisement, completed all 4 sensory testing sessions and were included in the longitudinal analysis. A total of 28 patients were recruited and finished the first session. After the first testing session, 5 patients dropped out, followed by 3 more after sessions 2 or 3. To be included in the investigation, patients were required on clinical examination by a gastroenterologist to meet Rome I

IBS Symptom Ratings

There were no significant changes in the mean values for self-rated IBS symptoms over the course of the 1-year study in either the total IBS sample (n = 20) or the PET subgroup (n = 12). Figure 1 shows the data for diary measures of symptom severity. Both samples had essentially unchanged symptoms over the 4 time points. There were no sex-related differences in these symptom reports in the total sample (14 females). Within-subject correlations for symptoms over the study year were also

Discussion

This study examined IBS symptoms, perceptual sensitivity to rectal distention, regional brain activation, and functional connectivity within distinct brain circuits longitudinally across multiple sessions of visceral stimulation over a 12-month period and compared these responses with healthy control subjects. It was aimed at evaluating the role of hypervigilance and underlying brain circuit activation in the visceral hypersensitivity of IBS patients. Although self-reported symptom severity and

Limitations and Conclusions

Several limitations of the current methodology should be mentioned. First, this study examined a heterogeneous sample of IBS patients including male and female patients with different predominant bowel habits. However, the fact that male and female patients showed nearly identical time courses of habituation of perceptual and emotional responses to the rectal stimulus over the 12-month period strongly suggests that the observed changes in brain activation are not a sex-related phenomenon.

References (60)

  • E.A. Mayer et al.

    Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis

    Pain

    (2005)
  • H. Mertz et al.

    Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention

    Gastroenterology

    (2000)
  • A. Ploghaus et al.

    Neural circuitry underlying pain modulationexpectation, hypnosis, placebo

    Trends Cogn Sci

    (2003)
  • B.D. Naliboff et al.

    Sex-related differences in IBS patientscentral processing of visceral stimuli

    Gastroenterology

    (2003)
  • E.A. Mayer et al.

    Sex-based differences in gastrointestinal pain

    Eur J Pain

    (2004)
  • J.T. Coull

    Neural correlates of attention and arousalinsights from electrophysiology, functional neuroimaging and psychopharmacology

    Progr Neurobiol

    (1998)
  • B.D. Naliboff et al.

    Evidence for decreased activation of central fear circuits by expected aversive visceral stimuli in IBS patients

    Gastroenterology

    (2000)
  • T. Lembo et al.

    Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome

    Gastroenterology

    (1994)
  • G. Bush et al.

    Cognitive and emotional influences in anterior cingulate cortex

    Trends Cogn Sci

    (2000)
  • P. Petrovic et al.

    Imaging cognitive modulation of pain processing

    Pain

    (2002)
  • B. Dickhaus et al.

    Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress

    Am J Gastroenterol

    (2003)
  • T. Lembo et al.

    Irritable bowel syndrome patients show altered sensitivity to exogenous opioids

    Pain

    (2000)
  • J.R. Augustine

    Circuitry and functional aspects of the insular lobe in primates including humans

    Brain Res Rev

    (1996)
  • S. Berman et al.

    Gender differences in regional brain response to visceral pressure in IBS patients

    Eur J Pain

    (2000)
  • S.J. Coen et al.

    Reproducibility of human brain activity following repeated oesophageal stimulation

    Gastroenterology

    (2003)
  • L. Yaguez et al.

    Brain response to visceral aversive conditioninga functional magnetic resonance imaging study

    Gastroenterology

    (2005)
  • M.D. Lieberman et al.

    The neural correlates of placebo effectsa disruption account

    Neuroimage

    (2004)
  • A.D. Wagner et al.

    Parietal lobe contributions to episodic memory retrieval

    Trends Cogn Sci

    (2005)
  • A.R. Hariri et al.

    Neocortical modulation of the amygdala response to fearful stimuli

    Biol Psychiatry

    (2003)
  • A.R. Hariri et al.

    The amygdala response to emotional stimulia comparison of faces and scenes

    Neuroimage

    (2002)
  • Cited by (0)

    Supported by NIH grants NR04881, P50 DK64539, R24 AT002681, and DK 48351 and funds from AstraZeneca R&D, Moelndal, Sweden.

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