Anybody who has ever battled through migraines knows just how agonizing they can be; however, nobody has ever figured out why the painful headaches persist as long as they do.

Until now.

University of Iowa researchers Paul Durham, Ph.D., a postdoctoral fellow in physiology and biophysics, and Andrew Russo, Ph.D., an associate professor of physiology and biophysics, have identified a feedback loop mechanism that could at least partially explain the prolonged nature of migraines. The UI researchers discovered that inflammatory agents released during a migraine might lead certain neurons in the head to increase the secretion of neuropeptides known as calcitonin gene-related peptides (CGRP). The CGRP then stimulates the release of additional inflammatory agents. This feedback loop results in continued secretion of CGRP and persistent pain for the person suffering the migraine.

"We are very interested in understanding the steps involved in controlling how CGRP is made and released from neurons during inflammation," Durham said. "Results from our research will likely identify potential therapeutic targets for the development of anti-migraine drugs that are more selective and potent than those currently available."

The UI investigators made their discovery while studying the anti-migraine drug called sumatriptan. Sumatriptan is the most effective anti-migraine drug currently available, alleviating migraine pain in 50 to 75 percent of patients. Although clinicians know that it works, they had not understood how it worked. Durham and Russo wanted to answer the questions of why CGRP levels were elevated during migraines and then how sumatriptan worked its migraine-zapping magic. Once they identified the feedback loop, the UI researchers were able to show that sumatriptan blocks this loop.

"The long-term goal of this finding is to take some of this information to drug companies so they can identify ways to make sumatriptan more effective or to develop n
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Contact: Jennifer Cronin
jennifer-cronin@uiowa.edu
319-335-9917
University of Iowa
15-Jun-1999