A woman in Scotland has been found to have a previously-unknown genetic mutation that makes her almost completely immune to pain, and on top of that her wounds heal faster and she seems to have generally reduced levels of anxiety and fear. Geneticists are now studying the genes responsible to see if they could lead to new potential treatments for pain relief.
Jo Cameron's pain insensitivity was discovered when, at the ages of 65 and 66, she underwent two surgical procedures – a hip replacement and an osteoarthritis operation on her hand. In both cases, she reported very little to no pain afterwards, even though both procedures are considered to be generally painful.
It turns out that this was a lifelong pattern for Cameron. When doctors asked about her everyday experiences with pain, she reported that minor cuts and injuries were usually painless – in some cases she didn't notice burns until she smelled burning flesh. She'd never needed painkillers after multiple varicose vein and dental procedures, and she'd even fractured a wrist and had a laceration stitched up without any pain whatsoever.
To find the root of her intriguing condition, Cameron was referred to pain geneticists at University College London and Oxford. Genetic analyses revealed two mutations that seemed to be responsible, centering on a gene known as FAAH, which has long been associated with pain sensation, mood and memory. One mutation seems to mediate FAAH expression, while the other controls the FAAH enzyme.
The first of those two mutations occurs in a gene that was, until now, thought to be non-functional "junk." The researchers have named this gene FAAH-OUT, since it suppresses FAAH and seems to be responsible for the reduced pain sensitivity. Interestingly, mice that have had the FAAH gene silenced also seem to have similar pain resistance.
But pain isn't the only thing affected: a silenced FAAH gene also seems to speed up wound healing, and helps with fear extinction – the ability for the brain to erase fearful memories. As a result, those with the mutation experience lower levels of anxiety in everyday life. In this case, Cameron got the lowest score on a common anxiety scale, and reportedly stays calm in stressful situations like a recent traffic incident she was involved in.
"We found this woman has a particular genotype that reduces activity of a gene already considered to be a possible target for pain and anxiety treatments," says James Cox, co-lead author of the study. "Now that we are uncovering how this newly-identified gene works, we hope to make further progress on new treatment targets."
It's not all beneficial though. Perhaps as a result of the ramped-up fear extinction, the woman reported frequent memory lapses throughout her life – mostly minor things, like forgetting a word mid-sentence or misplacing her keys.
The team also conducted genome analysis of Cameron's mother, daughter and son. Her mother and daughter don't seem to have the same pain resistance but her son does, albeit to a lesser extent. Interestingly enough, her son has the same FAAH-OUT mutation, but not on the second gene. Cameron says her late father also had little need of painkillers in life, leading the geneticists to suspect that she inherited the ability from him and passed it onto her own son.
Given that family line, and the fact that Cameron was unaware of her condition until her 60s, the researchers believe it's likely that other people have this particular mutation. Studying people like Cameron, and another family that was recently found to be completely immune to pain, could lead to new breakthroughs in pain relief.
"People with rare insensitivity to pain can be valuable to medical research as we learn how their genetic mutations impact how they experience pain, so we would encourage anyone who does not experience pain to come forward," says Cox. "We hope that with time, our findings might contribute to clinical research for post-operative pain and anxiety, and potentially chronic pain, PTSD and wound healing, perhaps involving gene therapy techniques."
Cameron herself is excited and hopeful to be part of the research.
"I would be elated if any research into my own genetics could help other people who are suffering," she says. "I had no idea until a few years ago that there was anything that unusual about how little pain I feel – I just thought it was normal. Learning about it now fascinates me as much as it does anyone else."
The research was published in the British Journal of Anaesthesia.
Source: University College London
