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At 71, She’s Never Felt Pain or Anxiety. Now Scientists Know Why.

来源:纽约时报    2019-04-01 06:03

        She had been told that childbirth was going to be painful. But as the hours wore on, nothing bothered her — even without an epidural.        有人告诉她,分娩会很痛。但随着生产过程的进行,她完全没有感到困扰——哪怕麻醉都没用。
        “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.”        “我能感觉到身体在变化,但并不觉得痛,”现年71岁的女子乔·卡梅伦(Jo Cameron)回忆说。她把整个过程比作“胳肢了一下”。之后,她还跟其他的准妈妈们说,“别担心,并不像大家说的那么可怕。”
        It was only recently — more than four decades later — that she learned her friends were not exaggerating.        直到最近——40多年后——她才知道她的朋友们并没有夸大。
        Rather, there was something different about the way her body experienced pain: For the most part, it didn’t.        相反,是她的身体对痛苦的感受异于常人:在大多数情况下,她感觉不到疼痛。
        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.        近100年来,科学家一直在记录那些很少感到疼痛或根本没有痛感的个案。但导致卡梅伦感受不到疼痛的基因突变,却是首次获得确认。
        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.        这项研究的进行,恰逢就如何负责任地治疗疼痛的激烈争论取得重大进展。周四,纽约州对萨克勒家族发起了迄今最大规模之一的法律诉讼,该家族拥有阿片类药物奥施康定(OxyContin)的制造商普渡制药(Purdue Pharma)。
        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.        “这些突变中每一种都教给我们一些东西,并指出一个特定的基因可能成为新的和更有效的止痛药的潜在目标,”他说。
        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.        导致科学家对卡梅伦的基因展开调查的一系列事件,始于约五年前。她说,她和丈夫在苏格兰的尼斯湖畔过着幸福平凡的生活。一次手部手术后,医生似乎感到很奇怪,她没有觉得疼,也不要止痛药。
        “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.        “我保证不需要任何东西,”卡梅伦记得自己对苏格兰北部一家医保医院的麻醉和止痛药顾问德夫吉特·斯里瓦斯塔瓦(Devjit Srivastava)说道。他也是这篇论文的作者之一。
        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.”        随后的一些问题显示,卡梅伦是不同寻常的。65岁时,她需要做髋关节置换。由于感受不到疼痛,等到她发现有异样时,情况已经非常严重。割伤、烧伤、骨折——这些都不会引起痛苦。事实上,她常常要等闻到皮肉烧焦的味道,或是丈夫看到她身上有血,才会注意到有什么地方不对劲。她还说,吃苏格兰圆帽辣椒只会造成“舒服的发热”。
        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.        最终,他在一个被科学家们称为FAAH-OUT的基因上找到了他所寻找的东西。我们都有这种基因,但在卡梅伦的病例中,“病人该基因的前半部分被删除了,”他说。他还说,进一步的血液研究证实了这一假设。
        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.        卡梅伦说,人们对她个案的兴趣令她意外。在和斯利瓦斯塔瓦交谈之前,她不太考虑疼痛这个问题。尽管她经常烧伤和割伤自己,她的伤口很少留下伤疤,这或许也很有帮助——科学家认为这也是和这种突变有关的。
        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.        已经有一些文章提到有类似情况的孩子的父母。许多父母生活在恐惧中,担心如果没有痛觉,他们的孩子就无法学会如何避免伤害自己。卡梅伦说,她的父母从来没有把这当成问题。她怀疑这可能是因为她从父亲那里遗传了这种突变。
        “I can’t remember him needing any painkillers,” she said. “I think that’s why I didn’t find it odd.”        “我不记得他吃过任何止痛药,”她说。“我想可能就是因为这样,我也不觉得这种事有什么奇怪的。”
        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.        科学家们对卡梅伦异常低的焦虑水平也很感兴趣。在焦虑障碍问卷调查中,她的得分是零(满分为21分)。她记不起自己曾经有过沮丧或害怕的感觉。
        “I am very happy,” she said.        “我很开心,”她说。
        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.        研究人员表示,他们现在的重点是更好地了解FAAH-OUT是如何工作的,这样他们就可以围绕FAAH-OUT设计一种基因疗法或其他疼痛干预措施。将这类发现转化为实际的疼痛或焦虑治疗需要很多步骤、很多年的时间以及大量资金。最终很少能得到实际产品。
        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.        但瓦克斯曼说这种事并不是没有先例。他提到他汀类药物,它们可以用来证明,具有不同寻常基因组成的个体可以塑造医学的未来。
        “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.        “这些药物的开发在很大程度上是因为发现了一些极其罕见的家族,在这些家族中,每个人都在20多岁时心脏病发作,”他说。卡梅伦或者其他人什么的基因突变是否可以决定止痛药的未来,现在下结论还为时过早。
        “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.        “但我有理由相信,我们从与疼痛有关的基因中学到的经验,将促使我们开发出一个全新的疼痛药物门类,”他说。

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