Biology

Unique genetic mutation found in family that doesn't feel pain

Scientists have isolated a genetic mutation that appears to render an Italian family unable to feel pain, and the find may help develop new treatments for people suffering chronic pain
Scientists have isolated a genetic mutation that appears to render an Italian family unable to feel pain, and the find may help develop new treatments for people suffering chronic pain
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Scientists have isolated a genetic mutation that appears to render an Italian family unable to feel pain, and the find may help develop new treatments for people suffering chronic pain
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Scientists have isolated a genetic mutation that appears to render an Italian family unable to feel pain, and the find may help develop new treatments for people suffering chronic pain

Unpleasant as it is, pain serves an important function by telling us that something is wrong. But for people suffering from chronic pain conditions, the message is blaring constantly, and conventional painkillers aren't all that effective. Now, a new hope for relief might have been found in the strange case of an Italian family, who all have a genetic mutation that makes them feel almost no pain at all.

The Marsili family are afflicted with a type of rare condition known as congenital analgesia or congenital insensitivity to pain (CIP), which means they don't feel pain as strongly as the average person. In some cases CIP-affected people grow up having never felt pain in their lives, and while that sounds like a good deal, it can be a huge problem. Anxious parents have to hover far more aggressively over a fearless child who never learnt the hard way not to touch a hot stovetop, and things like appendicitis, normally forewarned with severe pain, can go undiagnosed until the appendix actually bursts.

The six members of the Marsili family have a form of CIP so unique the condition has been named Marsili syndrome. A research team, lead by scientists at University College London (UCL), have conducted a genetic study into the family to determine the genetic root of the condition, how insensitive the family is to different types of pain, and whether the findings can be used to develop a new treatment for chronic pain.

"The members of this family can burn themselves or experience pain-free bone fractures without feeling any pain," says James Cox, lead author of the study. "But they have a normal intraepidermal nerve fibre density, which means their nerves are all there, they're just not working how they should be. We're working to gain a better understanding of exactly why they don't feel much pain, to see if that could help us find new pain relief treatments."

The UCL team clarified the family's "superpowers," and found that they're particularly insensitive to hot temperatures and capsaicin, the active component of chilli peppers that makes them spicy. The Marsilis have even fractured bones in the past without pain.

Next, the scientists conducted DNA tests from blood samples, and performed a whole exome sequence on each family member. This process lets them map out the protein-coding genes in the genome, and through that the scientists discovered that the Marsilis have a mutation in a gene known as ZFHX2. Surprisingly, this gene is normally very consistent across a wide range of species, and the team found that it is connected to other genes that are involved in pain signaling.

To determine how the gene is affecting pain response, the researchers ran two tests in mice. In the first experiment mice were bred with no ZFHX2 gene at all, and their pain thresholds were found to be altered. In the second test, mice were bred to have the same mutation as the Marsilis on that gene, and as a result these animals were insensitive to heat.

"By identifying this mutation and clarifying that it contributes to the family's pain insensitivity, we have opened up a whole new route to drug discovery for pain relief," says Anna Maria Aloisi, co-author of the study. "With more research to understand exactly how the mutation impacts pain sensitivity, and to see what other genes might be involved, we could identify novel targets for drug development."

Previous studies have identified other genes, such as SCN9A and PRDM12, that play a role in CIP and could be used to develop treatments for chronic pain. While they haven't yielded results yet, the researchers have hopes for ZFHX2.

"One possible treatment may be a gene therapy strategy, if we could find a way to mimic the Marsili phenotype by overexpressing the mutated transcription factor," says John Wood, co-author of the study.

The research was published in the journal Brain.

Source: University College London

3 comments
Imran Sheikh
pain is what stops us districting ourselves, we are blessed to have fully working pain receptors. else we are curious enough to go extreme, its pain receptors that stops us and sets the limit. though it would be a great discovery to cure some really painful conditions and cases.
Ralf Biernacki
Pain is a very needed sensation---it plays the same role as automatic machine stops in machinery, it stops us from exceeding safe parameters and injuring ourselves inadvertently. But to fulfill that function, pain does not need to be intense. Intense pain is debilitating, and can stop you from any rational response in an emergency situation. The optimal solution would be to genetically limit the intensity of experienced pain, so that it would still have its role as a warning signal, but could never rise to debilitating levels. So the best situation is halfway between the two extremes of no pain, and pain as we presently experience.
ripshin
Seems I recall a book entitled, "The Gift of Pain" or something similar, discussing this. I believe was related to leprosy...maybe... rip