The genes of the woman who can’t feel pain, mapped in detail

Scientists have figured out the mechanism of a rare genetic mutation that stops people from feeling pain – a discovery that might lead to improved painkillers.

Scottish woman Jo Cameron first sparked the interest of pain researchers in 2013, when her doctor found she didn’t need pain medications after major hip and hand surgery.

In 2019, they published the gene responsible, and called it FAAH-OUT.

Cameron had a rare mutation in her FAAH-OUT gene which, along with a mutation in another gene called FAAH, meant she barely felt pain, healed more quickly from injuries, and was less prone to anxiety and fear.

Now, the same team of scientists has established why this genetic mutation has caused these characteristics.

“The initial discovery of the genetic root of Jo Cameron’s unique phenotype was a eureka moment and hugely exciting, but these current findings are where things really start to get interesting,” says Professor James Cox, a researcher in medicine at University College London and senior author on a paper describing the research, published in Brain.

The researchers used CRISPR-Cas9 genetic modification experiments on lab-based cell lines to see how FAAH-OUT influenced other genes. They also looked at the expression of other genes to see which played a role in pain, mood and healing.

They found that FAAH-OUT regulates how the FAAH gene is expressed. When FAAH-OUT has Cameron’s mutation, it reduces the enzymes used and made by FAAH: it ‘turns the gene down’.

But it goes further than FAAH. The researchers found that Cameron’s two genetic mutations turn up another 797 genes, and turned down 348.

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These included genes related to wound healing and mood, possibly explaining Cameron’s low anxiety and fear.

“The FAAH-OUT gene is just one small corner of a vast continent, which this study has begun to map,” says senior author Dr Andrei Okorokov, also at University College London.

“As well as the molecular basis for painlessness, these explorations have identified molecular pathways affecting wound healing and mood, all influenced by the FAAH-OUT mutation.”

The researchers hope that these mapped genes will lead eventually to better treatments for a variety of things including pain, wound healing, and depression.

“By understanding precisely what is happening at a molecular level, we can start to understand the biology involved and that opens up possibilities for drug discovery that could one day have far-reaching positive impacts for patients,” says Cox.

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