VAI Voice

The official blog of Van Andel Institute
18 Apr 2019

The woman who doesn’t feel pain: A Q&A with Dr. José Brás

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We all know that being in pain is, well, a pain.

But despite the discomfort it brings, pain plays an important role in protecting the body by letting us know that something is wrong — a broken bone, a jagged cut, a disease disrupting normal function.

For one woman in the United Kingdom, however, pain isn’t part of the equation. She’s one of a group of people who feel little to no pain regardless of injury.

Her story was shared in late March by The Guardian on the heels of a study identifying the genetic mutation that shields her from the aches of everyday life and special agonies like those from an extensive hand surgery. Even more fascinating, the mutation also appears to give her an uncanny sense of calm in high-stress situations (like an accident two years ago that resulted in her car flipping into a ditch).

Dr. José Brás

We caught up with genetics expert Dr. José Brás, an associate professor in our Center for Neurodegenerative Science and study co-author, to discuss what they found, how it impacts health and how it could help treat pain in the future.

Q: Give us the short version. What did you study and what did you find?

JB: What we had was a person that did not feel much pain — she did feel some but that’s not always the case in these situations. She didn’t have any family history for this condition so it was particularly unusual because these things tend to run in families. When we studied her genes, we found one known genetic mutation and one new mutation that no one had found before.

This new mutation had immediate impact in that it lowers activity of an enzyme called FAAH. This leads to a series of things that result in a person having little to no pain sensitivity.

This is interesting because when we saw the mutation, there are aspects of the DNA sequence that suggest this phenomenon is likely more common than rare. This person wasn’t diagnosed until she was in her 60s, so it’s potentially likely that this happens more frequently than we thought. We all know people in our lives who feel pain more acutely than others and vice versa.

Q: This is a really cool finding. Does it have any therapeutic potential?

JB: We still need to understand a little bit more about how this mutation works. But we now have a target that we can try to modulate with drugs to make new analgesics, medications that make people feel less pain. It’s a novel target that we can try to hit for new therapies.

What’s also interesting is that this mutation happened spontaneously. That’s different than having a therapeutic intervention that is entirely manmade.

Q: The study also notes that this patient scored consistently low on stress and depression tests. Do you see potential for developing treatments for other conditions?

JB: There may be, particularly in depression and dementia. One thing that we’ve seen in the last few years is diseases that are very different often share the same or related molecular mechanisms. That’s what our evidence also suggests here.

Q: What’s next?

JB: We are still working with the team, which is led by investigators at University College London, to find other causes of this condition. They are working to understand how this gene works and the exact mechanism and function of this mutation. I’m extremely interested in its link to memory, especially in the context of Alzheimer’s disease.

Q: What should people remember about this finding?

JB: A couple of points — the understanding that these things exist is important and that genetics often plays an important role even if there is no family history for a condition. It’s amazing that a person can go through their entire life with something that has a strong genetic impact and never know about it.

 

Citation: Habib AM, Okorokov AL, Hill MN, Brás JT, Lee MC, Li S, Gossage SJ, van Drimmelen M, Morena M, Houlden H, Ramirez JD, Bennett DLH, Srivastava D, Cox JJ. 2019. Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity. British J Anaesthesia