Genes and migraine

Why do some people get migraine headaches while others do not? Researchers at the University of Iowa have discovered a particular genetic variation in people that may play an important role in susceptibility to migraines.

It has been suspected for quite some time that there are genetic reasons for who gets migraines and who does not, but the particular mechanisms were not clear. Based on their research findings, the University of Iowa research team believe that people who have migraines may have a subtle difference in the gene that is responsible for producing a certain small protein. That small protein is called RAMP1.

Don't be put off by the unfamiliar biochemical terminology here. The idea is actually quite straightforward.

RAMP1 appears to "turn up the volume" of a nerve cell receptor's response to another substance called CGRP. CGRP is thought to cause migraines. In fact, if it is injected into people who are susceptible to migraines, they get a severe headache or a full migraine.

CGRP levels are elevated in the blood during migraine, and drugs that either reduce the levels of CGRP or block its action significantly reduce the pain of migraine headaches.

RAMP1 is a key regulator of CGRP. Thus, people who have more RAMP1, also tend to be more sensitive to CGRP, which in turn causes them to have migraine headaches.

The University of Iowa team identified this link between RAMP1 and CGRP, and showed how a genetic variation in the amount of RAMP1 produced was related to sensitivity to CGRP, and ultimately to susceptibility to migraine.

Iowa researcher Dr. Andrew Russo said, "There is clearly a genetic difference between people who get migraines and those who do not, and we think that difference could be RAMP1. Our studies provide a reason to look for variations in the DNA that encodes RAMP1 in humans."

The UI team investigated CGRP receptors in the trigeminal nerve, which is responsible for relaying almost all sensory perception, including pain and touch, for the front of the head. The UI findings reinforce the emerging view that CGRP receptors in the trigeminal nerve play a key role in migraine headache.

However, there are other CGRP receptors throughout the body, and elevated CGRP levels are implicated in other types of pain, including arthritis. Russo predicts that his group's findings about RAMP1 will have implications for pain research beyond migraine headaches.[University of Iowa News Service]

The University of Iowa study was funded by the National Institutes of Health. The findings were published in the most recent issue of the Journal of Neuroscience.

Source: Zhang, Z., Winborn, C., Marquez de Prado, B., & Russo, A. (2007). Sensitization of Calcitonin Gene-Related Peptide Receptors by Receptor Activity-Modifying Protein-1 in the Trigeminal Ganglion. Journal of Neuroscience, Vol. 27, pp. 2693-2703.