Scientists are beginning to unravel the secret behind a woman’s pain-free life. In new research, a team in the UK has delved deeply into the genetic make-up of Jo Cameron, a woman in Scotland with a rare mutation that makes her virtually unable to feel physical and emotional pain. Among other things, the team found that her mutation appears to turn on and off a range of other genes, including those related to wound healing and mood.
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Researchers at University College London detailed Cameron’s story in 2019, although they first began investigating in 2013. At the age of 66, the woman had undergone hand surgery but, remarkably, did not require postoperative anesthesia afterwards. A year earlier, she was diagnosed with severe joint degeneration in her hip, but did not experience the pain she expected. She also reportedly felt little anxiety or fear throughout her life, and appeared to heal particularly quickly from cuts and bruises.
When UCL researchers examined them closely, they discovered two genetic mutations that seemed to explain their resilience, both linked to a pain-related enzyme called fatty acid amide hydrolase (FAAH). One was a deletion in a pseudogene (a region of DNA that resembles a gene but does not encode a protein) that the team later named FAAH-OUT; The other was in a gene close to the gene that actually regulates FAAH.
Other studies have found that FAAH plays an important role in controlling how we feel pain by breaking down a neurotransmitter that binds to our cannabinoid receptors. For example, studies on mice bred without the FAAH gene have shown that they feel less pain. But the woman’s unique condition — and the mutations that caused it — suggested that there are other ways our genes can affect pain sensitivity.
In a study published Tuesday in the journal Brain, the same UCL team is now getting closer to a better understanding of the underlying mechanisms behind the woman’s mutant powers.
Researchers used a variety of methods, including CRISPR gene-editing technology, to study the impact of the woman’s mutations on human biology. As expected, they found evidence that FAAH-OUT self-regulates the expression of FAAH. For example, your FAAH-OUT mutation appears to lower levels of the enzyme directly. But they also found that the mutation appears to turn hundreds of other genes on and off. Some of these genes affect how quickly we heal from wounds, while others affect our mood or levels of the body’s opioids. The results are also the latest to show that so-called junk DNA matters.
“The FAAH-OUT gene is just a small part of a vast continent that this study has begun to map. In addition to the molecular basis for painlessness, these investigations also identified molecular pathways that affect wound healing and mood, all of which are influenced by the FAAH-OUT mutation,” lead study author and UCL researcher Andrei Okorokov said in a university statement.
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Like any new discovery, these findings must be validated by others. And even a pain-free life doesn’t come without struggles. People with these conditions need to be extra careful not to overlook or overlook serious injuries, for example. But the lessons of Cameron’s genetics could well pay off in the future. Despite some initial promises, pain treatments based on directly affecting FAAH have not caught on. However, this research suggests there are other avenues to try and the UCL team are already planning to do so.
“As scientists, it is our duty to research this and I think these findings will have important implications for research areas such as wound healing, depression and more,” Okorokov said.