When she was eight years old, Jo Cameron broke her arm and didn’t tell anyone for days; it just wasn’t bothering her. In the six-odd decades since, she has sustained numerous injuries and felt barely any pain. Sometimes, she accidentally leans on her stove, only to notice when she smells burning flesh.
As Ian Sample reports for the Guardian, in investigation into the 71-year-old Scottish woman’s genes has led to the discovery of a previously unidentified mutation, which researchers believe plays an important role in pain signalling. The team who that sequenced and analyzed Cameron’s genome explain in the British Journal of Anaesthesia that the discovery could help pave the way for new chronic pain treatments.
For much of her life, Cameron didn’t realize that she was different. “I thought it was just me,” she tells Sample. “I didn’t know anything strange was going on until I was 65.”
It was then that Cameron sought out an X-ray of her hip, which would occasionally give way, but had not been causing her any pain. Doctors were stunned to see that her hip joint had severely deteriorated, and sent her for a hip replacement. After her surgery, the study authors write, she was briefly administered morphine. But when it caused severe vomiting, she got by on just two grams of paracetamol (also known as acetaminophen), a common medication used for moderate pain relief. On the evening after the operation, she scored her pain level as one out of ten.
While she was in the hospital, doctors noticed that Cameron’s thumbs had been badly affected by osteoarthritis, and she underwent a trapeziectomy to remove the bone at the base of the thumb. “Extraordinarily, she required no postoperative analgesics other than paracetamol for this known painful surgery,” the study authors write.
Intrigued, Cameron’s doctors sent her to pain specialists at University College London, who took a closer look at her DNA, along with that of her mother, son and daughter. In Cameron’s genome, they found a mutation in a region they dubbed FAAH-OUT, which, as Jacquelyn Corley explains in STAT, seems to ratchet down the activity of the neighboring gene FAAH.
FAAH breaks down anandamide, a neurotransmitter known as the “bliss molecule.” Anandamide binds with cannabinoid receptors in the brain and body—the same ones activated by the TCH in marijuana—and has been linked to a number of functions, including mood, memory and pain relief. If FAAH isn’t breaking down as much anandamide due to the mutation seen in Cameron’s genome, the molecule can build up in the body; Cameron was, in fact, “found to have more circulating levels of anandamide,” according to Corley.
This in turn might explain why Cameron doesn’t seem to feel pain the way that most people do. It would also explain other of Cameron’s reported traits. According to the study authors, she said she frequently experiences “long-standing memory lapses,” like forgetting words mid-sentence and misplacing keys. She also said that she never panics—not even in dangerous situations, like a recent car accident. Cameron’s mother and daughter do not share her pain insensitivity, but her son seems to have inherited it to a lesser degree.
Scientists have previously tried to relieve pain through drugs that inhibit FAAH, without any success. Targeting the newly pinpointed FAAH-OUT could offer “a new route to developing FAAH-related analgesia,” the researchers write. Their paper is, of course, rooted in only a single case study, and as Gizmodo’s Ryan F. Mandelbaum points out, more than one gene seems to influence pain sensitivity. The inability to feel pain among members of a family in Italy, for instance, has been linked to a mutation in the gene ZFHX2. Still, researchers are hopeful that Cameron’s case will offer new insights at a time when finding innovative ways to manage chronic pain has become a matter of critical importance.
“There’s an awful lot we can learn from her,” says study author James Cox, according to Sample. “Once we understand how the new gene works, we can think about gene therapies that mimic the effects we see in her. There are millions of people living in pain and we definitely need new analgesics. Patients like this can give us real insights into the pain system.”
For Cameron, living a relatively pain-free has its benefits—for one, as the study authors note, she can eat Scotch bonnet chilli peppers and feel nothing but a “pleasant glow”—but it also comes with downsides, like overlooking serious medical conditions because they don’t hurt. “It’s good in lots of ways but not in others,” she tells Sample. “I don’t get the alarm system everyone else gets.”
source: Smithsonian.com By Brigit Katz