Bowel-brain link may be key to diseases.

Bowel-brain link may be key to diseases

Researchers delving into the chemistry of the bowel have discovered a specific chemical link between the nervous system and the immune system. The discovery may lead to new treatments for such painful bowel diseases as ulcerative colitis and other inflammatory conditions.

The discovery has to do with the action of a neurotransmitter called substance P. The peripheral neurons that release substance P are thought to send pain signals to the brain and to help regulate the immune response in damaged tissues. The scientists, from the University of California at Los Angeles, the Harvard Medical School in Boston and the Veterans Administration Wadsworth Medical Center in Los Angeles, found that people with chronic inflammatory bowel diseases have high numbers of receptors for substance P in their intestinal tissue.

The scientists suggest the receptors cause disease when they short-circuit the normal response to intestinal distress. For example, the condition might start when a harmful bacterium or virus in the intestinal track interacts with a sensory neuron. The neuron, in turn, lets the body know something is wrong by both sending pain signals to the brain and releasing substance P into the tissues to mobilize the immune response. But in people with too many substance P receptors, the immune system seems to overreact, causing enough inflammation to trigger the sensory neurons to send more pain signals and release more substance P. "Something else may start the inflammation, but then it takes off on its own and gets caught in a loop," explains Patrick Mantyh of UCLA and Wadsworth.

The researchers, who report their results in the May PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES (Vol. 85, No. 9), found up to 2,000 times the normal density of substance P receptors and an irregular distribution of the receptors. "Normally, substance P receptors are just expressed on muscle tissue in the intestine," says Mantyh. "In tissue from chronically inflamed bowels, we found the receptors on blood vessels and immune cells, too."

The researchers are now trying to find a molecule that would block the substance P receptor and thereby interrupt the inflammatory cycle. Mantyh believes asthma and arthritis may also be caused by excess substance P receptors in the lungs and joints, and suggests that a receptor-blocking molecule might be used to treat those diseases.