U.S. Department of Health and Human Services

Pain expectations: altered brain responses in people with irritable bowel syndrome

A recent study suggests that people with irritable bowel syndrome (IBS) engage brain regions involved in threat appraisal and emotion more than healthy people do when facing an uncertain threat of pain.  IBS is a functional gastrointestinal disorder that is more common in women than in men.  People with IBS have chronic or recurring abdominal pain and altered bowel habits, such as constipation and/or diarrhea.  The cause(s) of IBS are unknown, but it is thought that multiple signals flowing in both directions between the brain and the gut (the “brain-gut axis”) play a major role in onset and recurrence of symptoms.  Studies have shown that when people with IBS are either told to expect or are actually undergoing a painful rectal stimulus, brain regions involved in pain processing and threat appraisal are much more active than they are in people without IBS.  At the same time, it is suspected that brain regions involved in emotional arousal contribute to symptom hypervigilance and visceral hypersensitivity in people with IBS. 

The new study investigated whether people with IBS show altered brain activity when uncertain about a future abdominal pain experience.  The pain experience used in the study was an electrical stimulation delivered via patch electrodes on the abdomen.  Prior to the experiments, the amount of stimulation to deliver to each individual was carefully tested to achieve a level that person considered unpleasant but tolerable.  Using imaging technology, researchers then looked at the brains of men and women with or without IBS under several repetitions of three conditions: when told verbally and with a visual cue that they may expect an unpleasant external stimulus to the abdomen within a certain time frame (“cued threat”); when told verbally and with a visual cue that there would be no stimulus within a certain time frame (“cued safe”); and when told verbally that there would be no stimulus, but without a visual cue about either the stimulus or the time frame (“uncued”).  The experiments were designed to increase the sense of ambiguity and the likelihood that anxiety would be heightened during the “uncued” condition, by alternating the “uncued” and “cued” conditions and leaving the electrodes attached to the abdomen at all times.  The scientists found that all participants showed activation of several brain regions in response to both the “cued threat” and the “uncued” condition when compared to the “cued safe” condition.  Compared to healthy people, however, people with IBS showed greater activity in brain regions involved in threat appraisal, emotional arousal, and self-consciousness during the “uncued” condition versus the “cued safe” condition.  This difference was primarily seen among women with IBS compared to their healthy counterparts.  Ambiguous situations generally lead the brain to engage in developing predictive responses, especially in those with anxiety, which occurs commonly in people with IBS.  These results provide clues into the role of brain response to context—i.e., uncertainty—in symptom experience, including symptom hypervigilance, in those with IBS.  Future studies should help to refine these findings and further flesh out the additional influence of sex and gender.

Hong JY, Naliboff B, Labus JS, Gupta A, Kilpatrick LA, Ashe-McNalley C, Stains J, Heendeniya N, Smith SR, Tillisch K, and Mayer EA. Altered brain responses in subjects with irritable bowel syndrome during cued and uncued pain expectation. Neurogastroenterol Motil 28: 127-138, 2016.