The GI Blues

It is the second leading cause of absenteeism from work in this country, trailing only the common cold. It affects 10% to 15% of the population, generating billions in medical bills every year. It traps many of its victims at home in the fear that they will be embarrassed by incontinence in public. Others commute to work in recreational vehicles so they will always have a bathroom handy.

It is called irritable bowel syndrome, and it is perhaps one of the least understood and least discussed afflictions in medicine. Many physicians who encounter these patients view the symptoms as psychosomatic. Even those gastroenterologists who recognize the disorder as a physical problem rather than a psychological one have few weapons to cope with it.

Many prescribe antispasmodic drugs to reduce colon activity, but “there is no evidence whatsoever that they reduce symptoms,” said Dr. Emeran A. Mayer of the West Los Angeles VA Medical Center and the UCLA Medical Center.

Understanding of the disorder, commonly called IBS, has recently undergone a major change, however--what scientists such as Mayer call a “paradigm shift.” Groundbreaking studies at UCLA have identified a unique biological mechanism in which nerve cells in the intestines are unusually sensitive to pain. Based in part on this discovery, at least 10 new drugs for the disorder are undergoing clinical trials at the VA Medical Center and one or more of them could be approved by the Food and Drug Administration in the next year.

Perhaps more important, Mayer and others are developing new knowledge of how the disorder arises, and that insight should lead to the development of a second wave of newer, more effective drugs within the next three to five years.

“We’ve really changed our way of thinking about [the disorder],” said Dr. Douglas Drossman of the University of North Carolina, “and that’s moved some of us toward new treatment strategies.”

“The tide is changing for us,” said Nancy J. Norton, founder of the International Foundation for Functional Gastrointestinal Disorders. The syndrome “is an area that was not addressed very thoroughly until five years ago,” when Mayer, Drossman and others began looking more carefully at it, she said.

“But there are still a lot of physicians, including gastroenterologists, who don’t know very much about the disorder,” she added. “We need to get the word out.”

The disorder is characterized by abdominal discomfort, bloating and abnormal bowel movements. Some patients suffer constipation, others suffer diarrhea and still others alternate between the two. The pain can often be quite severe, even disabling, but is usually relieved temporarily by passing gas or a bowel movement.

About two-thirds of patients who seek treatment are women, but Mayer and others believe that the disorder strikes men and women about equally. Anxiety and stress do not cause the disorder, but they can exacerbate the symptoms dramatically.

Past traumas may also contribute to a person’s susceptibility to the disorder, doctors believe, often triggering the first episode of the disorder. Drossman has found that 20% to 40% of women who seek treatment for the syndrome suffered sexual abuse as children. Nearly 80% of people with post-traumatic stress disorder also have the disorder, Mayer added.

Colon examinations, X-rays and CT scans usually show no physical abnormalities in the gastrointestinal system--a finding that has led many physicians to believe that the syndrome is psychosomatic.

The cause of the disorder, Mayer has found, may very well be in patients’ heads, but that cause is physical rather than psychological in nature. His studies strongly suggest that patients’ brains have difficulty filtering out routine sensory signals, including pain, from the intestine. The result is that people with this syndrome feel pain that others do not.

The gastrointestinal system has its own nervous system, sometimes known as the “small brain.” The small intestine is innervated by 100 million neurons, or nerve cells, as many as are found in the spinal cord. Tens of millions more control the esophagus, stomach and large intestine. Together, the gut has more neurons than the rest of the body.

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Mayer has demonstrated that in patients with the disorder, these nerves have a lower threshold for pain than those in healthy people.

Mayer, Dr. Dan Silverman and their colleagues demonstrated this by inserting a balloon into the rectum, intestine or another part of the gastrointestinal system. The balloon is inflated while brain activity is monitored with a PET scanner, which reveals the areas of the brain most active at any moment. Subjects are blindfolded so that they do not know whether the balloon is inflated.

Inflating the balloon in healthy people activates the brain’s anterior cingulate and the frontal cortex, the same areas that have been associated with the processing of painful sensations. Although the identical regions are activated in people with the disorder, the activation occurs at much lower pressures and over much larger areas of the brain, indicating that sufferers feel much greater pain.

When a healthy individual goes out to a restaurant, overindulges in a big meal, and perhaps drinks too much, he or she often suffers gastrointestinal distress and diarrhea, Drossman explains. The victim of the disorder, he said, “shows the same effects from a regular meal.”

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People with the syndrome also respond differently in anticipation of the pain. In healthy individuals, the anterior cingulate cortex and a region in the brain stem called the periaqueductal gray area are strongly activated when the subjects believe that the balloon will be painfully inflated. These areas are not activated in patients with the syndrome under comparable circumstances.

Mayer notes that the areas activated are particularly rich in receptors for endorphins, the body’s naturally occurring painkiller.

These endorphins, he speculates, normally screen out visceral sensations--sensations generated by the internal organs--unless there is unusual pain. The evidence so far, he says, suggests that it is this screening system that is somehow impaired in the disorder.

Mayer is confident that it will be possible to develop visceral analgesics, painkillers that block visceral sensations but not others.

“Within a year, clinical trials on the first wave of drugs [for the syndrome] will be over” and researchers will be able to design the second wave, he said. “We will know about the disease and what will work.”

For clinical information about irritable bowel syndrome:

https://www.ddc.org

or call the International Foundation for Functional Gastrointestinal Disorders at (414) 964-1799.