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Research uncovers promising target to treat chronic abdominal pain
Date:3/2/2009

et at it with these therapies," Stephens said.

The research is published in a recent issue of the American Journal of Physiology Gastrointestinal and Liver Physiology.

Stephens and colleagues tested the effects of higher-than-normal levels of EAAT2 in two different types of mice. They used mice genetically engineered to produce an excess of the protein as well as normal mice that were treated with an antibiotic already known to generate extra EAAT2 in the body. The transgenic mice had about twice the normal level of EAAT2, and those treated with the drug produced between 40 percent and 80 percent more of the protein than would a normal mouse.

Both the transgenic mice and mice treated with the antibiotic that increases EAAT2 experienced less pain than did control mice that had normal levels of EAAT2 in their system. In both types of mice with elevated levels of EAAT2, the pain response was reduced by approximately 50 percent to 70 percent compared to the pain levels in normal mice.

To further prove that EAAT2 was responsible for the reduced pain response, the scientists pretreated mice with dihydrokainate (DHK), a compound known to block the effects of that particular protein. The DHK significantly reversed the blunted pain response in mice with elevated levels of EAAT2.

Stephens said this approach appears to be effective for visceral pain only, and not for somatic pain, which is pain resulting from injuries to the skin, superficial tissues or muscles and bones.

The transgenic mice engineered to contain higher-than-normal levels of the protein are otherwise healthy. Stephens said that observation, combined with the fact EAAT2 does not affect somatic pain, suggest the protein is a good candidate for a therapy specifically designed to treat visceral pain.

"The drugs we have now aren't good. Really, all that's available is symptomatic treatment for irritable bowel syndrome. We just don't understan
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Contact: Robert Stephens
Stephens.6@osu.edu
614-292-4706
Ohio State University
Source:Eurekalert

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