Women with irritable bowel syndrome unable to regulate pain effectively

UCLA researchers have found that women who suffer from irritable bowel syndrome are unable to effectively turn off a pain-modulation mechanism in the brain, causing them to be more sensitive to abdominal discomfort than women without the condition.

The findings, which appeared in the Jan. 9 issue of the Journal of Neuroscience, may lead to a greater understanding of irritable bowel syndrome and new treatment approaches.

Irritable bowel syndrome affects 10 to 15 percent of the U.S. population and causes discomfort in the abdomen, along with diarrhea or constipation, or both. Currently, there is no cure for IBS, and treatments only lessen the symptoms.

"A large number of patients with irritable bowel disease suffer major decrements in their quality of life," said study author Dr. Emeran Mayer, professor of medicine, digestive diseases and physiology at the David Geffen School of Medicine at the University of California, Los Angeles. "Our research team studies the brain activity underlying the pain experience in patients with chronic pain disorders like IBS."

Previous research in the field has shown that the brain can prepare for pain in ways that either inhibit or amplify the sensory experience. When expected pain is predictable, tolerable and inescapable and will result in a reward — like a doctor’s injection to lessen its impact — most people’s brains limit the intensity of the pain experience. One way they do this is by decreasing the "gain" within the circuits that process the pain signal — similar to turning down the volume on a stereo — in order to make the body’s perception of pain less acute.

On the other hand, when the anticipated pain is perceived as escapable and potentially dangerous — such as burning one’s hand on a hot stove — most people’s brains will amplify the pain response in order to quicken reaction times and minimize possible injury.

The current study showed that IBS patients cannot turn down their pain response, even when the expected pain is not dangerous, making them highly sensitive to even mild discomfort.

UCLA researchers used functional magnetic resonance imaging (fMRI) to record the brain activity of 14 women with IBS and 12 healthy women during cued anticipation and a mild abdominal pain stimulus.

During pain anticipation, activity in the brains of subjects without IBS decreased in those areas involved with pain and emotional arousal — including the insula, amygdala and brainstem. IBS patients could not deactivate these circuits effectively, although they knew the pain was not dangerous.

"The abdominal hypersensitivity that is a hallmark of IBS may represent an inability to down-regulate pain and emotional-arousal circuits," said lead author Steven Berman, a senior research scientist at UCLA. "IBS patients may have an inability to inhibit the competing tendency to up-regulate emotional arousal in order to escape pain faster."

As expected, IBS patients reported lower pain thresholds and more anxiety than healthy women. Anxiety correlated with more brain activity during anticipation but not during the receipt of the pain stimulus.

"Negative emotions like anxiety and anger may interfere with the brain’s ability to strategically down-regulate pain-arousal pathways in situations where such an increased sensitivity is maladaptive," Berman said.

Activity in pain-arousal areas increased among both groups of women during the receipt of pain, but IBS patients showed greater boosts in several brain structures. The lower degree of anticipatory inhibition in arousal circuits was associated with more activity during the actual pain stimulus in executive cortical areas of the brain, which are associated with pain coping.

"We found that the lower the brain response during anticipation in the arousal circuits, the less the dampening effect of the cortex on pain sensitivity during the actual pain stimulus," Berman said.

Researchers note that describing this phenomenon in IBS leads to the classic chicken-and-egg debate: How much of the anticipatory brain dysfunction was produced by the long history of abdominal pain in patients, and how much did it predate and even cause their symptoms?

"Additional research may reveal that some pain patients have a primary difference in their brain’s reaction to pain," said Mayer, who also directs the UCLA Center for the Neurobiology of Stress. "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."

Several convergent findings from UCLA and other research groups support the importance of this research for better understanding IBS and other functional pain syndromes, including fibromyalgia and interstitial cystitis. Female patients show greater abnormalities than their male counterparts in this early brain response, and genetic factors have been identified which, together with early adverse life events, may predispose them to an altered responsiveness of emotional arousal circuits.

(Source: Journal of Neuroscience: Rachel Champeau: University of California, Los Angeles: January 2008)