At 71, She’s Never Felt Pain or Anxiety. Now Scientists Know Why.
She had been told that childbirth was going to be painful. But as the hours wore on, nothing bothered her ― even without an epidural.
“I could feel that my body was changing, but it didn’t hurt me,” recalled the woman, Jo Cameron, who is now 71. She likened it to “a tickle.” Later, she would tell prospective mothers, “Don’t worry, it’s not as bad as people say it is.”
It was only recently ― more than four decades later ― that she learned her friends were not exaggerating.
Rather, there was something different about the way her body experienced pain: For the most part, it didn’t.
Scientists believe they now understand why. In a paper published Thursday in The British Journal of Anaesthesia, researchers attributed Cameron’s virtually pain-free life to a mutation in a previously unidentified gene. The hope, they say, is that the finding could eventually contribute to the development of a novel pain treatment. They believe this mutation may also be connected to why Cameron has felt little anxiety or fear throughout her life and why her body heals quickly.
科学家认为，现在他们找到原因了。周四发表在《英国麻醉学杂志》(The British Journal of Anaesthesia)上的一篇论文中，研究人员认为卡梅伦几乎感受不到痛，是因为一种以前不了解的基因突变。他们说，希望这个发现最终能够为新型疼痛治疗的发展做出贡献。他们认为，这种突变还可能跟卡梅伦一生都不太会感到焦虑或恐惧，以及她的身体能很快痊愈之间有关系。
“We’ve never come across a patient like this,” said John Wood, the head of the Molecular Nociception Group at University College London.
“我们从未见过这样的病人，”伦敦大学学院(University College London)分子痛觉小组负责人约翰・伍德(John Wood)说。
Scientists have been documenting case studies of individuals who experience little or no pain for nearly 100 years. But the genetic mutation that seems to be responsible for Cameron’s virtual painlessness had not been previously identified.
The study emerged amid major developments in the emotionally charged debate over how to responsibly treat pain. On Thursday, New York state filed one of the most sweeping legal cases yet against the Sackler family, which owns Purdue Pharma, the maker of the opioid OxyContin.
And it was yet another reminder that we need less addictive alternatives for chronic pain, said Dr. Stephen G. Waxman, a neurologist at Yale and author of “Chasing Men on Fire: The Story of the Search for a Pain Gene.” Waxman was not involved in the recent paper but he also studies people who have rare mutations that alter their experience of pain.
耶鲁大学的神经学家、《追火者：寻找疼痛基因的故事》(Chasing Men on Fire: The Story of the Search for a Pain Gene)一书的作者斯蒂芬・G・瓦克斯曼博士(Stephen G. Waxman)说，这再次提醒我们，在慢性疼痛治疗上，我们需要不具成瘾性的替代药品。瓦克斯曼没有参与最近的这篇论文，但他对那些拥有罕见突变的人也有研究，这种突变改变了他们的疼痛体验。
“Each of these mutations teach us something, and point to a particular gene as a potential target for new and more effective pain medications,” he said.
The sequence of events that led scientists to investigate Cameron’s genes began about five years ago. She was living a happy, ordinary life on the banks of Loch Ness in Scotland with her husband, she said. After a hand operation, a doctor seemed perplexed that she was not experiencing any pain and did not want painkillers.
“I guarantee I won’t need anything,” Cameron recalled telling Devjit Srivastava, a consultant in anesthesia and pain medicine at a National Health Service hospital in northern Scotland and one of the authors of the paper.
A few follow-up questions revealed that Cameron was unusual. At 65, she had needed to have her hip replaced. Because it had not caused her pain, she had not noticed anything was amiss until it was severely degenerated. Cuts, burns, fractures ― these did not hurt either. In fact, it often took the smell of burning flesh or her husband identifying blood for her to notice something wrong. She also reported that eating Scotch bonnet chili peppers left only a “pleasant glow.”
Srivastava referred her to University College London’s Molecular Nociception Group, a team focused on genetic approaches to understanding the biology of pain and touch. They had some clues for her. In recent decades, scientists have identified dozens of other people who process pain in unusual ways. But when Dr. James Cox, a senior lecturer with that group and another author of the new paper, inspected her genetic profile, it did not resemble that of others known to live without pain.
斯里瓦斯塔瓦把她介绍给伦敦大学学院(University College London)的分子痛觉小组，该组织专门使用遗传学方法来理解痛觉和触觉生物学。他们在她身上找到一些线索。近几十年来，科学家们已经发现了几十个以不同寻常的方式感知疼痛的人。但是，该研究小组的高级讲师、这篇新论文的另一位作者詹姆斯・考克斯(James Cox)博士检查她的基因图谱时，发现她的基因与其他已知生活中没有痛觉的人的基因并不相似。
Eventually he found what he was looking for on a gene the scientists call FAAH-OUT. All of us have this gene. But in Cameron’s case, “the patient has a deletion that removes the front of the gene,” he said. Additional blood work confirmed this hypothesis, he said.
Cameron said she had been shocked by the interest in her case. Until her conversation with Srivastava, pain was not something she thought about. Perhaps it helped that even though she burned and cut herself quite often, her injuries rarely left scars ― something else that scientists believe is connected to the mutation.
A number of articles have been written about parents of children with similar conditions. Many live in fear that without pain, their children won’t learn how to avoid hurting themselves. Her parents never made it an issue, she said. She suspects this may be because she inherited the mutation from her father.
“I can’t remember him needing any painkillers,” she said. “I think that’s why I didn’t find it odd.”
Scientists are also intrigued by Cameron’s extraordinarily low anxiety level. On an anxiety disorder questionnaire, she scored zero out of 21. She cannot recall ever having felt depressed or scared.
“I am very happy,” she said.
The researchers said they would now focus on trying to better understand how FAAH-OUT works so that they can design a gene therapy or other pain intervention around it. Turning a discovery of this sort into an actual pain or anxiety treatment requires many steps, many years and many millions of dollars. It’s rare for a product to emerge.
But it’s not unprecedented, Waxman said. As a reminder of how an individual with an unusual genetic makeup can shape the future of medicine, he pointed to statin drugs.
“They were developed largely on the basis and discovery of incredibly rare families where everyone was having heart attacks in their 20s,” he said. Whether it will be Cameron’s mutation or another individual’s mutation that directs the future of painkillers, it’s too early to say.
“But I’m reasonably confident that the lessons we are learning from the genes involved in pain will lead to the development of an entirely new class of pain medications,” he said.