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

Abstract

Background A majority of subjects with irritable bowel syndrome (IBS) 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. Methods A task-dependent functional magnetic resonance imaging technique was used to investigate the brain activity of 37 healthy controls (18 females) and 37 IBS subjects (21 females) during: 1) a cued expectation of an electric shock to the abdomen versus a cued safe condition; and 2) an uncued cross-hair condition in which the threat is primarily based on context versus a cued safe condition. Key Results 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, IBS 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. Conclusions & Inferences The observed greater engagement of cognitive and emotional brain networks in IBS subjects during contextual threat may reflect the propensity of IBS subjects to overestimate the likelihood and severity of future abdominal pain.

Learning by experience? Visceral pain‐related neural and behavioral responses in a classical conditioning paradigm

“…These findings are in line with our second hypothesis and support the notion of partially overlapping central mechanisms underlying nocebo effects induced by verbal suggestions and classical conditioning, particularly encompassing cingulate, prefrontal, and somatosensory networks. The contribution of pACC and dlPFC to attention, cognitive appraisal, and top‐down inhibitory control is well established in the broader pain field as well as in visceral pain and IBS . Together with existing work from the somatic pain field, our findings in visceral pain suggest this pain‐modulatory system to be involved across pain modalities.…”

“…The contribution of pACC and dlPFC to attention, cognitive appraisal, and top-down inhibitory control [40][41][42][43] is well established in the broader pain field 44,45 as well as in visceral pain and IBS. 21,46,47 Together with existing work from the somatic pain field, our findings in visceral pain suggest this pain-modulatory system to be involved across pain modalities.…”

Sex Differences Linking Pain-Related Fear and Interoceptive Hypervigilance: Attentional Biases to Conditioned Threat and Safety Signals in a Visceral Pain Model

“…Hence, increased attention to interoceptive, visceral sensations may lead to the exacerbation of symptoms and distress (82) in line with the fear avoidance model, which has yet to be more fully tested in the context of chronic visceral pain and the gut-brain axis. Neuroimaging studies support this assumption by demonstrating increased functional connectivity in the salience network in IBS patients during resting state (83), rectal stimulation (84) and contextual threat situations (85). Initial support that the behavioral modification of attentional bias may improve attentional functioning and regulation of brain mechanisms related to anxiety and attention in IBS patients (86,87), provides a treatment perspective to complement more basic mechanistic research.…”

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…[52] IBS patients exhibit hyperactivity in the amygdala and connected brain regions both at baseline and in response to visceral stimulation. [53,54] In some studies at least, sex and genetic differences have been identified in IBS-induced amygdala hyperactivity, and stronger effects are observed in males [55] and those with a particular polymorphism of the serotonin receptor gene, HTR3A. [56] Overall, amygdala hyperactivity seems to be related to chronic visceral hypersensitivity, pointing to another important link between the gut and the amygdala.…”