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Gene that could be associated with reduced pain response found

Gene that could be associated with reduced pain response found

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Researchers found an Italian family, the Marsilis that have six individuals who respond significantly differently to pain than others. This includes a 78-year-old lady and her two daughters and their three children. They suspected that this family might have a different genetic configuration that could be altering their response to pain. According to them, this could be a new path to developing medications for chronic pain. The study appeared in the latest edition of the journal Brain.

Study’s lead author, Dr James Cox from UCL Wolfson Institute for Biomedical Research, said that the members of this family were literally free of pain. He explained that these people can burn themselves or break a bone without feeling any pain. One of the girls for example, broke a bone skiing and continued doing so without realizing her injury.

However, on closer examination the team noted that the pain fibres or the nerves that lie within the top layers of the skin are same as any other normal person with equal density and abundance. They noted that these nerves however did not work as they should. He said the team was working towards understanding why they did not respond similarly to pain and this could help the scientists find new approaches to pain medications. They add that at least one in 10 persons experience severe and disabling chronic pain. However, the treatments are still limited to the common painkillers or NSAIDs.

In this study, the researchers obtained the DNA samples from the individuals of this family to understand their genetic makeup and differences from others. There has been previous research on the genetics of this family and this unique phenomenon that describes their response to pain is termed, “Marsili syndrome” after their surname. These individuals are not responsive to heat, breakage of bones and also exposure to capsaicin that is present in chilli peppers.

On mapping out the genetic sequences of these individuals, it was noted that protein coding genes of genomes of each of the family members showed a variation at a point called the ZFHX2 gene. Because of this mutation there is a difference in the protein that this gene codes for. This protein is same across different species of animals including mice and frogs.

To understand the genetic mutation better the researchers went on to conduct two animal experiments in the lab on mice. They bred mice that did not have the ZFHX2 gene and saw that these mice did not respond to pain like other normal mice. They further caused mutations in the ZFHX2 gene similar to the Marsili family genetic sequence. Now they noted that the mice were significantly resistant to high temperatures feeling little or no pain. They speculated that this specific gene could be regulating other genes that could play a role in signaling of pain sensations to the brain.

Co-author Professor Anna Maria Aloisi from University of Siena said that identification of this mutation could open up a new avenue in pain management and relief. This could lead to identification of “novel targets for drug development,” she said. Professor John Wood from UCL Wolfson Institute for Biomedical Research and co-author of this study added that there could be gene therapy in future for pain relief if the researchers could, “find a way to mimic the Marsili phenotype by overexpressing the mutated transcription factor.” Study’s first author, Dr Abdella Habib from Qatar University, College of Medicine, who conducted the study while at UCL said that more research projects can help find, “better treatments for the millions of people worldwide who experience chronic pain and don’t get relief from existing drugs.”

The study received its funding from Medical Research Council, Wellcome, and Arthritis Research UK among others.

Reference: https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awx326/4725107

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