UI researchers begin to unravel the underlying mechanism of migraines

June 15, 1999

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 new drugs," Russo said.

What surprised Durham and Russo was how sumatriptan worked. Sumatriptan caused an unusually prolonged increase in the calcium levels of the affected neurons, known as trigeminal neurons. Usually, increases in calcium are associated with increased peptide secretion, not decreased secretion, which is the case with CGRP.

"We believe the calcium is like a light switch," Russo said. "If you just flick the calcium on high and then switch it off quickly, it causes increased secretion. But when it works like a dimmer switch set halfway, it inhibits secretion. It is a beautiful illustration of the complexity of our body's cells. The cells can take the exact same signal and, depending upon its amplitude and duration, get completely opposite results."

In the big picture, the UI findings are important because they provide biochemical evidence of the basis of migraines. Because sumatriptan blocks the CGRP release from neurons in complete absence of any vascular contribution, this indicates that the key regulators are the neurons.

Durham and Russo are now trying to identify the enzymes that stimulate the initial CGRP secretion.

"Although our study has yielded some very interesting results, it is important to realize that we are still a ways away from treatment," Russo said. "We need to continue to study the process to fully understand when, why and how it occurs."
-end-
The UI findings appear in a recent issue of the Journal of Neuroscience. The work was supported by grants from the National Institutes of Health and the American Heart Association.



University of Iowa

Related Neurons Articles from Brightsurf:

Paying attention to the neurons behind our alertness
The neurons of layer 6 - the deepest layer of the cortex - were examined by researchers from the Okinawa Institute of Science and Technology Graduate University to uncover how they react to sensory stimulation in different behavioral states.

Trying to listen to the signal from neurons
Toyohashi University of Technology has developed a coaxial cable-inspired needle-electrode.

A mechanical way to stimulate neurons
Magnetic nanodiscs can be activated by an external magnetic field, providing a research tool for studying neural responses.

Extraordinary regeneration of neurons in zebrafish
Biologists from the University of Bayreuth have discovered a uniquely rapid form of regeneration in injured neurons and their function in the central nervous system of zebrafish.

Dopamine neurons mull over your options
Researchers at the University of Tsukuba have found that dopamine neurons in the brain can represent the decision-making process when making economic choices.

Neurons thrive even when malnourished
When animal, insect or human embryos grow in a malnourished environment, their developing nervous systems get first pick of any available nutrients so that new neurons can be made.

The first 3D map of the heart's neurons
An interdisciplinary research team establishes a new technological pipeline to build a 3D map of the neurons in the heart, revealing foundational insight into their role in heart attacks and other cardiac conditions.

Mapping the neurons of the rat heart in 3D
A team of researchers has developed a virtual 3D heart, digitally showcasing the heart's unique network of neurons for the first time.

How to put neurons into cages
Football-shaped microscale cages have been created using special laser technologies.

A molecule that directs neurons
A research team coordinated by the University of Trento studied a mass of brain cells, the habenula, linked to disorders like autism, schizophrenia and depression.

Read More: Neurons News and Neurons Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.