Brain response differences found in way women with irritable bowel syndrome deal with pain

UCLA researchers found that women with IBS cannot effectively turn-off a pain modulation mechanism in the brain, which causes them to be more sensitive to abdominal pain, compared to women without IBS.

The findings, appearing in the January 9, 2008 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 and/or constipation. Currently there is no cure and treatments only lessen symptoms.

“A large number of patients with irritable bowel disease suffer major decrements in their quality of life,” said Dr. Emeran Mayer, study author and professor of medicine, digestive diseases and physiology, David Geffen School of Medicine at UCLA.. “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, inescapable and will result in a reward -- like a doctor's injection to improve your health -- most people tell their brain to inhibit the intensity of the pain experience. One way they do this is by turning down the gain within brain circuits that process the pain signal --- similar to turning down the volume on a stereo amplifier -- in order to make the body's perception of pain less acute.

When anticipated pain is perceived as escapable and potentially dangerous – such as burning your hand on a hot stove – most people tell their brain to amplify the pain response, which is like increasing the volume on a stereo amplifier, in order to react faster and minimize possible tissue damage.

The current study showed that IBS patients cannot turn down the amplifier of the pain response, even when expected pain is not dangerous, which makes them more sensitive to even mild discomfort.

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

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

“The abdominal hypersensitivity that is a hallmark of IBS may represent an inability to downregulate pain and emotional arousal circuits, said Steven Berman, lead study author and a senior research scientist at UCLA. “IBS patients may have an inability to inhibit the competing tendency to upregulate 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 receipt of pain.

“Negative emotions like anxiety and anger may interfere with the brain's ability to strategically downregulate pain arousal pathways, in situations where such an increased sensitivity is maladaptive,” said Berman.

Both groups of women increased activity in pain arousal areas during receipt of pain, but IBS patients showed greater boosts in several brain structures. The lower degree of anticipatory inhibition was associated with more activity during pain 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,” said Berman.

Researchers note that explaining 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 cause their symptoms?

“Additional research may reveal that some pain patients have a primary difference in their brain's reaction to pain,” said Mayer, director of 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 converging findings from UCLA and other research groups support the importance of this research for better understanding IBS and other functional pain syndromes, such as fibromyalgia. Female patients show greater abnormalities than their male counterparts in this early brain response, and genetic factors have been identified which may predispose to an altered responsiveness of emotional arousal circuits.

The study was funded by the National Institutes of Health (NIDDK and NCCAM) and in part by Novartis Pharmaceuticals. Dr. Mayer has received research grants from Novartis and has previously served as a consultant.