Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>A majority of the subjects with irritable bowel syndrome (<jats:styled-content style="fixed-case">IBS</jats:styled-content>) show increased behavioral and brain responses to expected and delivered aversive visceral stimuli during controlled rectal balloon distension, and during palpation of the sigmoid colon. We aimed to determine if altered brain responses to cued and uncued pain expectation are also seen in the context of a noxious somatic pain stimulus applied to the same dermatome as the sigmoid colon.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A task‐dependent functional magnetic resonance imaging technique was used to investigate the brain activity of 37 healthy controls (18 females) and 37 <jats:styled-content style="fixed-case">IBS</jats:styled-content> subjects (21 females) during: (i) a cued expectation of an electric shock to the abdomen <jats:italic>vs</jats:italic> a cued safe condition; and (ii) an uncued cross‐hair condition in which the threat is primarily based on context <jats:italic>vs</jats:italic> a cued safe condition.</jats:p></jats:sec><jats:sec><jats:title>Key Results</jats:title><jats:p>Regions within the salience, attention, default mode, and emotional arousal networks were more activated by the cued abdominal threat condition and the uncued condition than in the cued safe condition. During the uncued condition contrasted to the cued safe condition, <jats:styled-content style="fixed-case">IBS</jats:styled-content> subjects (compared to healthy control subjects) showed greater brain activations in the affective (amygdala, anterior insula) and attentional (middle frontal gyrus) regions, and in the thalamus and precuneus. These disease‐related differences were primarily seen in female subjects.</jats:p></jats:sec><jats:sec><jats:title>Conclusions & Inferences</jats:title><jats:p>The observed greater engagement of cognitive and emotional brain networks in <jats:styled-content style="fixed-case">IBS</jats:styled-content> subjects during contextual threat may reflect the propensity of <jats:styled-content style="fixed-case">IBS</jats:styled-content> subjects to overestimate the likelihood and severity of future abdominal pain.</jats:p></jats:sec>