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P&S Journal

P&S Journal: Fall 1995, Vol.15, No.3
Clinical Advances: By Lynne Christensen
Attacking Irritable Bowel

llustration by David Rosenzweig
Contrary to a commonly held belief that irritable bowel syndrome is the physical manifestation of a nervous personality, researchers at P&S believe a physical cause precedes psychological factors. Although the specific physical cause has not been identified, researchers suspect the syndrome stems from an abnormality in the enteric nervous system (the part of the autonomic nervous system that controls the digestive track). The key to understanding irritable bowel syndrome appears to lie at the cellular level, with the role of the neurotransmitters such as serotonin in the enteric nervous system (ENS) and with the development of the ENS at the embryonic stage.

Irritable bowel syndrome affects nearly one-third of all Americans. There is no cure and no single, effective treatment. This poorly understood syndrome is being studied by P&S researchers on two fronts. While Dr. Michael Gershon, professor and chairman of anatomy and cell biology, works toward a better understanding of the cellular actions of the enteric nervous system, a new Center for Intestinal Dysfunction will study and evaluate irritable bowel syndrome.

The symptoms of irritable bowel syndrome can include abdominal bloating, bowel irregularity, and abdominal cramping. Although the syndrome is rarely life-threatening, it can severely diminish quality of life. "This is not a fatal disease; it is a miserable disease," says Dr. Joseph Sweeting, professor of clinical medicine, who co-directs the Center for Intestinal Dysfunction with Dr. Susan L. Lucak, assistant professor of clinical medicine.

While research is under way in the lab to identify the cause of irritable bowel syndrome and to develop targeted therapies, the Center for Intestinal Dysfunction offers patients a compassionate place to be evaluated and to receive the best treatments available. Often patients with irritable bowel syndrome go from doctor to doctor for batteries of diagnostic tests, only to be told the problem is in their head, not their intestines.

At the center, patients are evaluated by a multidisciplinary team consisting of a gastroenterologist, psychiatrist, and nutritionist. If necessary, patients also may see an allergist and a specialist in bowel motility. The goal is to establish the diagnosis and prescribe a course of treatment after two or three sessions with the team.

On the basic science level, the vast complexity of the ENS, which contains more neurons than the rest of the peripheral nervous system combined, is only now beginning to be untangled. It is expected

that as this work progresses and the neurologic network of the ENS is better understood, new treatments for digestive ailments, such as irritable bowel syndrome, could be developed.

Although the ENS is a distinct branch of the autonomic nervous system, a major part of the peripheral nervous system, it more closely resembles the brain and differs both physiologically and structurally from any other region of the peripheral nervous system. The factors responsible for the development of the unique properties of the ENS remain unknown, but progress is growing in understanding enteric neuronal development. Dr. Gershon's research is focused on describing the actions of the enteric nervous system at the cellular level.

Dr. Gershon and colleagues have identified the critical role played by the neurotransmitter serotonin in gastrointestinal motility. For example, studies have shown that individuals with irritable bowel syndrome often respond differently to hor- mones released by the upper gastrointestinal tract. The researchers hope their work will eventually translate into more highly targeted drug therapies.

"We need to stop thinking in terms of drugs that will block neuromuscular transmission," says Dr. Gershon. "That approach is too gross. You can stop all the diarrhea in the world if you give enough atropine and paralyze the gut, but nobody will thank you for it. What we have to do is think of the neurons that are involved more subtly in regulation, and there are many, many types. Knowing what those neurons are will help us come up with effective drugs."

To achieve his research aims, Dr. Gershon is reaching all the way back to the processes involved in the embryonic development of the ENS. By examining the neural crest, the transient structure that forms in embryos, Dr. Gershon has identified two regions from which cells migrate to the gut and colonize it. Researchers have identified molecules that promote the differentiation of cells to become enteric neurons or ganglia as opposed to peripheral neurons or ganglia.

Dr. Gershon's work suggests that digestive ailments may begin at the developmental stage with an abnormality in the ENS then are exacerbated by psychological factors. Both Dr. Sweeting and Dr. Lucak theorize that mental condition is not the principal cause of irritable bowel syndrome. Says Dr. Sweeting, "It may be made worse by the mental state, but the disorder comes first."

copyright ©, Columbia-Presbyterian Medical Center

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