Pain of Irritable Bowel Syndrome Traced to the Brain

By John Gever
LOS ANGELES, Jan. 9 -- The source of the pain of irritable bowel syndrome may be abnormal brainstem function, researchers here said.
Patients with irritable bowel syndrome showed heightened activity in brain areas responsible for pain sensation and emotional arousal when they anticipated abdominal pain from certain stimuli, even though patients knew the stimuli were not dangerous, reported Steven Berman, M.D., of UCLA, and colleagues, in the Jan. 9 issue of the Journal of Neuroscience.
Anxiety about irritable bowel symptoms is itself one of the condition's most important symptoms, said Dr. Berman and colleagues said, noting that it can exacerbate the severity of physical symptoms, including pain. Altered neurological preparation for expected pain is one explanation for this effect, which is what they set out to explore in their study.
The investigators studied 14 women with irritable bowel syndrome and 12 healthy women. Participants underwent a balloon-driven rectal distention procedure that causes no tissue damage but creates sensations of pressure. The procedure included a light-based visual cue to signal the start. Distentions of 25 and 45 mm Hg were induced, as was a sham distention of 5 mm Hg.
Questionnaires administered just prior to the procedure confirmed that the irritable bowel syndrome patients were more anxious, angry, and stressful beforehand than the healthy individuals. The patients had mean scores of 6.0 for stress, 6.0 for anxiety, and 5.8 for anger at baseline. Corresponding values for controls were 3.2 (P<0.0001), 2.5 (P<0.0001) and 2.4 (P=0.0002).
During the procedure, activity in participants' insula, amygdala, and brainstem was monitored with functional MRI.
Among the most notable findings was the response to the visual cue. The healthy controls showed widespread decreases in brain activity. Dr. Berman and colleagues interpreted this reaction as downregulation of pain-signaling systems, which is a normal response to anticipation of unpleasant sensations consciously understood as innocuous or inescapable.
In contrast, no such decrease in brain activity was seen in the irritable bowel syndrome patients. This indicates that the patients "are more anxious and less able than healthy controls to downregulate activity" associated with anticipated pain, especially in the dorsal brainstem where much of this regulation is centered.
Patients with irritable bowel syndrome also showed stronger brain reactions to the actual rectal distention, relative to controls. At 45 mm Hg, for example, activity cluster scores in the anterior insula among patients were 620 on the left side and 540 on the right. Among controls, the corresponding values were 264 and 279.
A similar pattern occurred with the smaller distentions, but the differences were less pronounced and affected fewer brain areas. In the sham distention, none of the differences reached statistical significance.
On the basis of their findings, Dr. Berman and colleagues concluded that noradrenergic regulation in the brainstem is disrupted in irritable bowel syndrome, although they said more studies are needed to confirm the mechanism.
"Additional research may reveal that some pain patients have a primary difference in their brain's reaction to pain," said Emeran A. Mayer, M.D., another UCLA researcher who worked on the study. "If we can identify receptors and genes associated with these abnormal brain responses, we should improve both identification of predisposed patients and development of effective remedies."
The findings may also have implications for the underlying pathology and possible treatments for fibromyalgia and other chronic pain syndromes.
An estimated 10% to 15% of the adult population in the U.S. has irritable bowel syndrome, about three-quarters female.
Funding for the study was provided by the National Institutes of Health and Novartis Pharmaceuticals.
Dr. Mayer has received research grants from Novartis and has previously served as a consultant.
Primary source: Journal of NeuroscienceSource reference:Berman S, "Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome" J Neuroscience 2008; 28: 349-59.