A woman in Scotland has lived an extraordinary life, almost entirely free of physical pain, anxiety, or fear, and it may be because of a pair of genetic mutations.
In a new research paper published in the British Journal of Anaesthesia by a team of doctors from several institutions including the University College London (UCL), a 71-year-old woman is reported to have lived nearly all of her life with an extreme insensitivity to pain, as well as having almost no experiences of anxiety, fear, or depression.
Researchers believe that this is the consequence of a mutation in a previously-unidentified pair of genes that may be directly tied to the human pain response and that response’s associated connection to fear, anxiety, and depression.
"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," said Dr James Cox of UCL and one of the lead researchers for the study. "Now that we are uncovering how this newly-identified gene works, we hope to make further progress on new treatment targets."
Doctors Discover Her Pain Insensitivity Late in Life
It wasn’t until the age of 65 that this woman learned that her almost entirely pain-free existence was abnormal. She had gone in to see a doctor about an issue with her hip and the doctors found severe degeneration in the joint, all the while she had no experience of what should have been severe pain.
"The implications for these findings are immense."—Dr Devjit Srivastava, National Health Service
A year later, she underwent surgery for her hand which, considering that our hands are necessarily one of the more nerve dense parts of our bodies, is normally very painful. Again, no experience of post-surgical pain. She reported never having to take any sort of pain-killer after operations such as dental surgeries.
Dr Devjit Srivastava, Consultant in Anaesthesia and Pain Medicine at an NHS hospital in Northern Scotland was the one to diagnose her extreme pain insensitivity, and co-authored the paper describing their findings.
She was sent to a pain geneticist at UCL who conducted genetic analyses and identified two mutations that stood out. One was what the researchers called a microdeletion in a pseudogene, only briefly annotated prior to this case and largely ignored. This gene, called FAAH-OUT by researchers in their paper and described in detail for the first time, was also paired with a mutation in a neighboring gene that governed the FAAH enzyme.
This second gene had long been known to pain specialists for its connection to the endocannabinoid signaling that is essential to pain sensitivity, as well as memory and mood.
"The implications for these findings are immense," said Dr Srivastava.
Targeting the Genetic Blueprint For Pain Response
In laboratories, scientists have seen in mice that do not have the FAAH gene experience reduced pain sensitivity, faster wound healing, reduced anxiety, and enhanced fear-extinction memory. When describing her life experience, the woman in the study reports almost identical experiences and behavior.
She reported that she could be burning herself on a stove and would only realize that she had burned herself by the smell of burnt flesh. She tested as having the lowest score possible on a common anxiety scale and reported periods of memory lapse that the researchers tied to enhanced endocannabinoid signalling.
"We hope that with time, our findings might contribute to clinical research for post-operative pain and anxiety,” said Dr Cox, “and potentially chronic pain, PTSD and wound healing, perhaps involving gene therapy techniques".
As for the woman, she hopes that her experiences are able to help develop new treatments. “I had no idea until a few years ago that there was anything that unusual about how little pain I feel,” she said. “I just thought it was normal. Learning about it now fascinates me as much as it does anyone else."
“I would be elated if any research into my own genetics could help other people who are suffering,” she added.