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What is Calcitonin Gene-Related peptide – CGRP? Part 2

In order to understand how researchers are working to discover new Migraine specific treatments and how they might work to help us, we need to learn about one of the newest targets: CGRP. A brief explanation of CGRP basics may be found here on Part 1.

In Part 2 it is helpful to explain how CGRP works in its receptors. This is one spot researchers have been looking particularly closely hoping to find a treatment

Locks and Keys

An easy way to explain the basics of how these receptors work is to picture a lock and a handful of keys.

Normally a lock will have a specific key that will both fit into the hole, and turn the lock to create an action — if it’s a door, the lock opens and the door handle is free to turn to open the door. In this case CGRP fits into its receptor like a key which turns on our pain.

In our analogy, other keys may fit into the hole but not turn the lock. So long as those other keys remain inside the hole, it is impossible to put the right key into the hole because the lock has been *blocked*. It was hoped that blocking CGRP from its receptors like this would help to control the debilitating pain of Migraine.

Researchers are looking at antagonists that will keep the CGRP from working, but they are also looking at antibodies (immune cells) that will target and eliminate CGRP — a good example of how researchers can use one bit of information like the function of CGRP, to think outside the box.

As you can see, these are not Migraine cures as current headlines might overstate, but potential treatments and preventives. Of course what we all dream of is a cure, but this is important too.

Baby Steps

There has been a drug compound that was found to block CGRP receptors. When trialed as an acute treatment (to be taken during an attack) there was success with few side effects. However when it was trialed as a preventive it caused elevated liver enzymes which was considered a serious side effect. As a result, the drug Telcagepant was subsequently abandoned as useful to Migraineurs. This was a disappointing setback, but researchers learn important things from both setbacks and successes.

There was mention of CGRP at the American Headache Society’s Annual Scientific Meeting in Los Angeles this past June, the most interesting words I heard spoken outside of the presentations. Headache specialists and researchers expressed disappointment in the failure of Telcagepant and seemed concerned that they would find a way to utilize this new target.

Work continues however, and so long as there are researchers looking for ways to trick this system into making our lives more worth living, Migraineurs have hope.

Baby steps are small, but so long as they are in the forward direction we’re making progress.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.

Merck. “Insights into the pathophysiology of migraine.” Migraine Resources. Copyright © 2009–2010 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. • Durham, Paul, PhD. and A. Russo (2003). “Stimulation of the calcitonin gene-related peptide enhancer by mitogen-activated protein kinases and repression by an antimigraine drug in trigeminal ganglia neurons“. J Neurosci 23 (3): 807–815. PMID 12574409 • Durham, Paul, PhD. (2006). “Calcitonin Gene-Related Peptide (CGRP) and Migraine”. Headache. 46 (1): S3–S8. PMCID: PMC3134175 • Durham, Paul, PhD., Cady, Roger, MD and R. Cady (2004). “Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy“. Headache 44 (1): 35–42. doi:10.1111/j.1526-4610.2004.04007.x. PMID 14979881


  • Dee
    6 years ago

    Thanks Ellen! This research in particular gives me alot of hope. Your posts are always so relevant and forward thinking!

  • Ellen Schnakenberg author
    6 years ago

    Dee, It’s so easy for us to feel overwhelmed, and one of the major obstacles we have to climb re: our disease is the feeling of hopelessness that leads to depression. I was at that hopeless place once, and I never want another patient to feel like that. So, I am sooooo happy that this piece gave you some little piece of hope to look forward to. They say hope is stronger than fear… I tend to agree 🙂

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