Nerve Cell Receptor Linked to Bowel Disease

Duke researchers prevent colitis in rat experiments

Gary Gately

Gary Gately

Published on May 09, 2003

FRIDAY, May 9, 2003 (HealthDayNews) -- Blocking the action of a nerve cell receptor that appears to trigger intestinal inflammation could lead to development of new treatments to prevent inflammatory bowel disease.

That's the conclusion of a study by Duke University researchers, who say they have found in rats a specific nerve cell receptor that appears to initiate the inflammation that leads to colitis, a type of inflammatory bowel disease (IBD).

The receptor, called the vanilloid receptor type 1 (VR-1), is stimulated by acid, heat and the chemical capsaicin, which puts the "hot" in red hot chili peppers. Thus, when you eat chili peppers the VR-1 receives and transmits the sensations of pain and heat.

Shutting down the action of the VR-1 in the rats prevented colitis, and the same process could prevent IBD in humans, says the study, in the May issue of Gut.

Lead researcher Dr. Christopher Mantyh says chemicals produced when the immune system senses a threat to the body's well-being cause the inflammation, a hallmark of colitis.

Previous research has centered on discovering a viral or bacterial trigger, says Mantyh, a colorectal surgeon and assistant professor of surgery at Duke University Medical Center. The Duke researchers, however, focused on preventing activation of the VR-1.

"If you blocked the VR-1 receptor, what you're doing is preventing the chain reaction, so the bacteria or toxin or whatever it is [activating the receptor] may be in your body, but if it can't stimulate the VR-1 receptor, it's essentially harmless," Mantyh says.

"I think this is a novel way of looking at how inflammation can occur in the colon," says Mantyh, a colorectal surgeon and assistant professor of surgery at Duke. "This provides some insight into what may be some of the early events in the inflammatory cascade in the intestines."

IBD, which Mantyh says afflicts some 3 million Americans, includes an array of chronic disorders in which the intestine becomes inflamed, usually causing abdominal cramps, pain and diarrhea, sometimes bloody.

In the study, researchers divided the rats into three groups with about 10 in each. One group got capsaicin at birth, stimulating the VR-1 receptors to the point of inactivating them permanently. The second group -- adult rats -- received a VR-1 antagonist called capsazepine to block the VR-1 receptor, and a control group received no treatment.

All the rats then received a chemical that would normally induce colitis.

After a week, the control group rats had colitis, but the rats in the other two groups had significantly lower levels of the disease, the study found.

Ulcerative colitis accounts for about half of IBD cases in humans, while the other half are Crohn's disease, Mantyh says, but he adds that researchers believe blocking the VR-1 could help prevent both conditions in humans.

How to safely block the VR-1 in humans remains unclear, Mantyh says. Any drug that blocks an immune system function -- in this case, inflammation -- can be risky, he says, to the point that even a cold could become a major illness because of a compromised immune system.

Mantyh says follow-up studies could lead to a way to shut off the VR-1 in humans without danger.

Dr. R. Balfour Sartor, a professor of medicine in the Department of Microbiology and Immunology at the University of North Carolina, Chapel Hill, says the findings could open the door to possible drug therapy for IBD.

But Sartor adds the colitis induced in the rats more closely resembles acute inflammation, not the chronic inflammation that characterizes the disease in humans.

Mantyh says the seven-day duration of the disease would be the human equivalent of somewhere between acute and chronic disease. And he says researchers hope to do a longer study.

Sartor also says the rodent model has limited applications for humans and that the study's focus on prevention alone leaves unanswered how the research would apply to the chronic cases physicians treat.

"It's a lot easier to prevent the onset of disease than to reverse established disease, which is what you do in clinical treatment," Sartor says.

"It's interesting, but not earth-shattering," he says of the Duke study. "It's absolutely something that needs to be further investigated."

More information

For more on inflammatory bowel disease, visit the Crohn's & Colitis Foundation of America or the American Academy of Family Physicians.

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