内容来源：https://www.quantamagazine.org/how-does-touch-lead-to-pain-or-pleasure-20260806/

内容总结：

触摸如何通向疼痛或愉悦？神经科学揭示皮肤与大脑的深层奥秘

疼痛与愉悦看似是生活中最直接的感受，但神经科学界至今仍难以解释：为何生理性疼痛与心理性疼痛感受不同？为何爱人的抚摸令人安心，而陌生人的触碰却让人抗拒？围绕这些根本性问题，哥伦比亚大学祖克曼研究所的神经科学家伊斯梅尔·阿卜杜斯-萨布尔博士近日接受播客节目《探索之悦》专访，分享了他在触觉与疼痛研究领域的前沿成果。

疼痛：进化赋予的生存信号

阿卜杜斯-萨布尔指出，疼痛并非单纯的负面体验，而是生物体进化出的重要保护机制。他提到，历史上曾发现罕见家族因基因突变完全丧失痛觉，但这些患者往往因无法感知危险而早年受伤甚至夭折。这说明疼痛对生存至关重要。

在实验室中，如何测量动物是否感受到疼痛是一大挑战。由于动物无法用语言描述感受，研究人员通过“条件位置厌恶”等行为学实验来推断其痛觉体验——如果动物能记住并回避曾接受有害刺激的环境，便说明其具备一定的疼痛认知能力。

分子层面：特定受体决定感觉类型

过去二十余年，疼痛研究迎来分子革命。2001年诺贝尔生理学或医学奖得主大卫·朱利叶斯发现了感知辣椒素和热量的TRPV1受体，而阿德姆·帕塔普蒂安则发现了感知机械压力的Piezo受体。这些发现表明，不同感觉由特定的分子受体介导，并激活截然不同的神经通路。

阿卜杜斯-萨布尔实验室致力于填补从皮肤感知到大脑认知之间的空白。他坦言，目前医学界尚无客观的疼痛生物标志物，临床仍依赖患者自述。“我们正在寻找，但至今没有一种基因或脑区激活能确切告诉我们某个人是否处于疼痛状态。”

愉悦触觉：皮肤中的“快乐神经”

除了疼痛，阿卜杜斯-萨布尔还研究令人愉悦的社交性触摸。他的团队发现了一类特殊的触觉神经元，它们仅对温柔的抚摸产生反应，并激活大脑奖赏回路，释放多巴胺。这种通路在缓解压力、焦虑和抑郁方面可能具有巨大潜力。

“当你在低落时得到亲人一个拥抱，真的会感觉好起来。”他说，“我们正在揭示这条从皮肤到大脑的通路如何工作，未来或可通过激活皮肤中的特定神经元来治疗脑部疾病。”

裸鼹鼠：几乎不痛、长寿、极度社交的奇迹生物

阿卜杜斯-萨布尔还分享了他在裸鼹鼠上的研究。这种东非地下啮齿动物几乎不感知多种疼痛，不易患癌，寿命长达30至40年，且几乎没有衰老迹象。更神奇的是，裸鼹鼠是哺乳动物中社会性最强的物种——一个群落可容纳数百只个体，由唯一“女王”繁殖，群体成员几乎时刻保持身体接触。

“它们大部分感觉皮层都用于处理触觉，”他说，“我们相信它们是触觉专家，可能用触摸完成其他动物靠视觉完成的交流与识别。”研究裸鼹鼠或能为理解人类长期稳定社会关系提供独特视角。

伦理与未来：在动物研究与人类福祉间平衡

面对动物实验的伦理争议，阿卜杜斯-萨布尔态度坦诚：“我们理解动物为人类福祉做出牺牲，因此尽量使用最少数量的动物，并尽可能减轻它们的痛苦。”他认为，在目前缺乏更优替代模型的情况下，动物研究仍是理解疼痛机制和开发慢性疼痛疗法不可或缺的环节，但他也期待未来计算机模拟或类器官模型能够部分替代动物实验。

科学之美：发现与传承的喜悦

谈及科研中最大的快乐，阿卜杜斯-萨布尔提到两类时刻：一是“顿悟瞬间”——比如他的实验室最近在哺乳动物泌乳反射中发现了关键的触觉神经元，“那感觉就像全世界只有我们几个人知道了一个秘密”；二是指导学生成长，“帮助他人实现梦想，和发现一样令我兴奋。”

他最后强调，要真正理解疼痛、愉悦与意识，神经科学家需要与心理学家、认知科学家携手合作。“我们都在研究大脑和心智，但两个领域对话太少。只有跨学科融合，才能真正解开这些终极谜题。”

中文翻译：

触摸如何导致疼痛或愉悦？

引言

疼痛和愉悦似乎只是生活中简单的事实，然而它们远非如此。神经科学家至今仍无法解释，例如，为什么身体疼痛与心理疼痛不同，或者为什么所爱之人的触摸能带来安慰，而陌生人的触摸却令人反感。

为了探索这些感觉背后的科学，贾娜·莱文采访了哥伦比亚大学祖克曼研究所的神经科学家伊斯梅尔·阿卜杜斯-萨布尔。他们的对话涵盖了疼痛如何服务于进化目的、研究人员在缺乏任何客观生物标志物的情况下如何在实验室中测量疼痛和愉悦，以及触摸如何作为一种社交和情感信号而不仅仅是感官信号发挥作用。阿卜杜斯-萨布尔还描述了他对裸鼹鼠的研究——这种动物几乎感觉不到疼痛，没有衰老迹象，并且生活在几乎完全建立在触摸之上的群体中——以及在研究无法描述自身感受的动物时涉及的伦理权衡。

可在Apple Podcasts、Spotify、TuneIn或您最喜欢的播客应用上收听，也可以从Quanta网站流媒体播放。

文字记录

[音乐播放]

贾娜·莱文：你好。外面的听众朋友们好，我是贾娜·莱文。

史蒂夫·斯特罗加茨：我是史蒂夫·斯特罗加茨。

莱文：这里是《为什么的乐趣》。

斯特罗加茨：一档来自《Quanta杂志》的播客，我们在其中探讨当今数学和科学领域一些最大的未解问题。

莱文：史蒂夫，我们一直在与伊斯梅尔·阿卜杜斯-萨布尔交谈，他是哥伦比亚大学的教授，离我只有几个街区远，我们谈到了皮肤作为一个器官，以及作为传递愉悦和疼痛的媒介。

斯特罗加茨：嗯哼。听起来很有意思。

莱文：是的。我觉得很有意思的是，人们对疼痛的了解非常少。我的意思是，如果你想想自己的经历，当你开始思考这个问题时，会觉得有点奇怪。它到底是什么呢？它非常令人不快，但除此之外，它是什么？

斯特罗加茨：这真的很神秘，尤其是当你遇到的疼痛与组织损伤没有真正关联的时候。比如，有时我只是在厨房水槽边洗东西，然后突然感到疼痛，我就会想，“拜托，这太荒谬了。我没对我的背做什么。”而且，你知道，人们会告诉你疼痛是心理上的。你可以通过自我劝说摆脱某些疼痛，这就提出了一个观点：疼痛并不像乍看起来那么简单。

莱文：是的，特别是，他在动物层面研究这个问题。但这是那些动物很难可靠地告诉你它们正在经历什么的事情之一。所以，他的很多工作实际上是在努力解读动物的内心世界，即动物对不同感觉的体验。

斯特罗加茨：是的，我在你描述这项工作时想到，触摸是了解内心世界的手段，还是触摸本身就是这里的主要研究对象？

莱文：我觉得这是个有趣的问题。就像许多科学抱负一样，当然，或许大的目标是意识，对吧？但事实上，大的目标总是遥不可及的。那不是他们所使用的语言。

他们所使用的语言是数据、观察。你知道的，这对他们的实验来说更直接。

斯特罗加茨：嗯，对。人们说科学是可解问题的艺术，所以我们要把自己限制在能够取得进展、取得真正进步的事情上。

但我必须说，当你提到愉悦和疼痛时，我有一点不安的感觉，尤其是作为一个家里养着动物的人。我的狗，默里，我那么爱它。

莱文：是的，我听说过默里。

斯特罗加茨：我知道。我相信大家都听说过。

莱文：我看过默里的照片。

斯特罗加茨：好吧。好吧。但即便如此，我的意思是，想到疼痛，你知道，我知道我们的听众中有很多动物权利倡导者。所以，我希望在听这期节目时，我不知道，疼痛这部分会讲些什么？

莱文：我们确实谈过这个。我的意思是，这是一个非常温和的动物爱好者。和伊斯梅尔交谈真的很有意思。他的实验，它们很温和。也许，他们会注意到爪子是否缩回，所以如果感到不适，但他们不会折磨这些动物。

但即便如此，我认为动物实验，即使是在最温和的意义上，也会受到质疑。他也在思考其中的伦理问题。

那么，让我介绍一下我们的嘉宾。他叫伊斯梅尔·阿卜杜斯-萨布尔。他是附近的哥伦比亚大学祖克曼研究所的神经科学家，研究皮肤-大脑轴，特别是我们的触觉，包括轻柔的触摸和抚慰性的触摸。

斯特罗加茨：太棒了。

[音乐播放]

莱文：欢迎来到《为什么的乐趣》，伊斯梅尔。很高兴能和你交谈。

伊斯梅尔·阿卜杜斯-萨布尔：能和你在一起也是我的荣幸。

莱文：能在同一个大校园里认识同事，真是令人愉快。我很想从你的经历开始聊起。你在费城长大。我读过你的一些其他采访，你在其中谈到你对动物的热爱，以及你曾经如何把你家的三楼变成了一个为期一年的科学实验。也许我有点夸张了，但请告诉我你小时候与动物最初的接触。

阿卜杜斯-萨布尔：是的。是的，能来这里真的很开心，我想，如果你问我小时候想做什么职业，我总是说我想成为一名科学家。你知道，我并不直接认识任何科学家，但如果我想起学校的课程，那些让我感到非常兴奋和充满活力的课程，而且我小时候经常看《动物星球》，我可以连续看几个小时的自然节目。

我成长过程中养过很多宠物，狗和猫，还有蜥蜴、乌龟和蛇。你知道，我记得小时候订阅过一本叫《乌龟文摘》之类的杂志。你知道，我对生物学和生物系统，以及动物如何沟通和合作非常着迷。我认为我的科学生涯是在高中一年级认真开始的，正如你所提到的，在费城的中央高中，作为荣誉生物学课程的一部分。你知道，实际上，我们没有上体育课，因为要报名参加这个荣誉生物学课程，我们必须上两节生物课。对我来说，即使作为一个14岁的孩子，我也毫不犹豫地抓住了这个机会。你知道，谁需要体育课呢？确实被取笑了一点。

但是，你知道，作为那个项目的一部分，我们有机会做一个长达一年的科学展览项目，很多学生在费城附近的大学工作，比如天普大学、德雷塞尔大学或宾夕法尼亚大学。但我们也可以在家做科学实验。所以这就是我做的。你知道，用基本的简陋设备和东西。这个项目实际上是研究小龙虾的再生。

所以，你知道，我的父母非常支持我，让我接管了我们在费城日耳曼敦区的房子的三楼。你知道，那里有几百只小龙虾，我敢肯定那上面味道不太好。但在当时，你知道，社会上非常流行补充剂和人参之类的东西。人参被认为是一种神奇的补充剂，可以改善健康和记忆力，还有各种奇妙的好处。

所以我的想法是，如果我在小龙虾的水里加入这种人参草药补充剂，那么这可能会加速再生的速度，因为它们确实有能力再生失去的附肢。所以，你知道，我得以成为一名科学家，我修剪它们附肢的一部分，并测量它重新长出来的速度。那是一段非常令人兴奋的时光，可以写实验笔记本，有可以测试的假设，制作图表，绘制数据，进行统计检验来看看是否有任何发现。

不幸的是，我不太记得那些结果了。

莱文：你没有像现在这样认真地做数据分析。

阿卜杜斯-萨布尔：是的，完全正确。就是这样。

莱文：我们实际上有共同点。我的女儿痴迷于动物，有一次我们在纽约市的公寓里养了大约23只动物。看起来就像个宠物店。有蛇、蜥蜴、狼蛛。简直疯了。只有一次发生动物杀死动物的事情。我觉得，这种对动物的兴趣是一种真正的召唤。

但您最终选择研究较小尺度的生物学，细胞、分子层面。是什么促使您从这种对动物的热爱转向了实际的更微观层面的生物学？

阿卜杜斯-萨布尔：当我上大学时，我想，你知道，又是这种对动物的热爱，也许我想成为一名兽医。

所以我在许多兽医诊所和医院工作过，在那里我的经历是帮助兽医做绝育手术，而且非常单调，坦率地说，相当无聊。我有点怀念那种快节奏的生物探索性质。所以我在大学三年级时在宾夕法尼亚大学细胞与发育生物学系做了另一个实习，在那里我们研究小鼠心脏中的细胞，呃，嗯，小鼠心脏中对心脏发育和功能很重要的蛋白质。

在那里我接触到了分子生物学研究和实验室工作，以及科学文化，整个科学学科的精神气质，比如实验室会议，人们展示结果，讨论所有未解决的问题，能够从分子、DNA、RNA，生命的分子的尺度来看待生命。

我觉得那非常令人兴奋。直到几年后，我才进入神经科学和感觉神经科学领域。

莱文：是的。有一段有趣的历史，痛苦的经历——请原谅我的双关——关于我们与动物的关系，以及那种否认动物有意识或会感到疼痛的观点。

阿卜杜斯-萨布尔：是的。

莱文：呃，所以回到17世纪的笛卡尔，他臭名昭著地进行活体解剖，当活着的动物嚎叫时。他怎么可能——我并不是要求你为这个观点辩护——但他怎么可能提出动物没有感觉疼痛呢？

您如何理解我们是如何从这种身体上的超脱——正如我们的一位《Quanta》同事所说，“它们不思考，所以它们不存在”——过渡到接受动物会感到疼痛的观点的？

阿卜杜斯-萨布尔：这是一个很好的问题，也是我思考了很多的问题，并且让我和实验室里的每个人都夜不能寐。我的意思是，这是一个更广泛问题的一部分，即意识问题，对吧？动物是否拥有我们所拥有的那种意识水平？

所以，如果我们把这个问题归结为疼痛的概念以及它如何运作，以及我们在哪里划定动物是否感到疼痛的界限？这是一场持续多年的争论，我认为现代的观点是，你需要一个大脑，你需要某个中央处理单元来拥有完整的功能和认知才能体验疼痛。

如果你看看较低等的动物，也许没有人否认它们能感知伤害感受。伤害感受是一个花哨的术语，指的是外周神经系统中的受体、神经元，它们可以被有害刺激激活。这些信号会传送到某些中央处理单元，以便动物知道要躲开。我认为这个观点，每个人都理解。甚至简单的细菌，对吧，单细胞生物，如果你把它们放在一个不适宜的环境中，它们会移开。它们会退缩，因为它们有外周神经系统中的感觉神经元。

现在，我们会认为那是伤害感受，但不完全是疼痛。要概括疼痛的体验，你必须有一个中央处理单元，使你能够适当地响应后续的有害刺激。有某种学习和记忆。有更高层次的认知。你明白我收到的这个特定刺激会让我疼痛，所以现在我要避开它。

那么争论就在于，如果是这样的话，哪些动物有这种能力，哪些动物没有？我认为，作为神经科学界，总的来说，观点一直是许多动物，尤其是较低等的动物，可能没有那种更高层次的认知和意识。

你知道，我经常被问到的一个问题是，尤其是新英格兰地区的人，他们会问关于龙虾的问题，对吧？我是否应该为把这只活龙虾扔进滚烫的锅里而感到内疚？

莱文：慢煮龙虾的经典例子。

阿卜杜斯-萨布尔：完全正确，但人们会说，“嗯，他们告诉我它们感觉不到疼痛，所以我不应该感到内疚。”然后他们问我，“这是真的吗？”这取决于你问谁，对吧？也许你必须做测试。

所以作为一个领域，我们做的经典测试叫做条件性位置厌恶。也就是说，动物是否有足够的“脑力”来理解这个东西是有害的？它们应该能够理解它们受到有害刺激的环境是不好的。这样如果你稍后把它们放在那个环境中，它们能记住“我在这里收到的某些东西是不好的，我想要逃离或避开它”。

那些没有这种认知能力的动物，尽管它们会对有害的东西退缩。它们没有能力形成记忆、意识感知、那种被归因于疼痛的负面感受，对吧？

这就是人们所做的，如果你能通过这个测试并表明它们能建立这些联系，那么人们就会说，“你知道吗？我认为这种动物能感到疼痛，让我们把这种动物加到名单上。”

莱文：这很有趣，因为你专门研究的动物必须感到疼痛才能成为你研究的一部分，但同时也感受不到疼痛。这也是你研究的一部分。为什么它们感受不到——我们稍后会谈到裸鼹鼠。

阿卜杜斯-萨布尔：是的。我们主要研究啮齿类动物，我认为人们普遍接受啮齿类动物能体验疼痛或伤害感受。它们会缩回爪子，就像我们会缩回手一样。在我们的领域中，关于疼痛的更高层次组成部分，即与疼痛相关的情绪负面效价，存在一些争论。啮齿类动物在多大程度上体验这些？

这就是我认为我一些工作重要性的部分原因，因为我们以非常详细的动物行为图谱来追踪动物在经历不同刺激时的表现。我们可以说，它们确实以某种方式做出反应，它们无法向我们描述它们持续的情绪状态，但如果我们能使用行为作为它们内部状态的读数，它们展示出的行为非常具有疼痛负面情绪状态的特征，我们正在试图在大脑中绘制这个图谱。

莱文：你提出的这个问题非常有趣，因为在阅读你的工作时，我一直在想心理疼痛与身体疼痛有何不同。除了不同之外，它们又是如何相互关联的，对吧？正如你描述的，如果动物没有心理成分，我们就会在严重程度上降低它的等级。

阿卜杜斯-萨布尔：这是非常正确的。而且你知道，我认为很多时候我们低估了动物的智力或认知，因为我们不知道如何深入其中。我们还没有设计出正确的测试。

你让我想起了我一位同事的工作，加州大学圣地亚哥分校和索尔克研究所的凯·泰教授。她在啮齿类动物中研究了这个问题：身体疼痛和情绪、心理疼痛是否在大脑中的任何地方有对应或交叉？她设计了一个非常巧妙的测试，她称之为小鼠的FOMO任务，即“错失恐惧症”，她让小鼠住在一起。然后她在它们之间放了一个隔板，隔板外的动物必须坐在那里看着它的朋友们喝巧克力奶昔。

所以，这只老鼠只是看着它的朋友们。这只老鼠有点饿，有点渴，看着朋友们喝奶昔。她的想法是，这类似于一种心理形式的疼痛。然后她在大脑中被称为岛叶皮层的区域进行记录，并提出这样的问题：这是否与身体疼痛相互作用？看起来确实如此。就像在经历这种情绪心理疼痛之后，它改变了它们对身体疼痛作出反应的门槛。也许大脑中存在类似的构造，我们甚至可以在啮齿动物中研究这一点。

莱文：让我们讨论一下其中涉及的一些实际科学。那么，你在躯体感觉系统中的研究涉及疼痛、触摸和皮肤。你能告诉我一些不同的感觉类型所涉及的大脑通路和不同受体吗？

阿卜杜斯-萨布尔：当然。对，正如你提到的，躯体感觉系统是我们的感觉系统，它介导触觉、痛觉、痒觉、温度、压力。

莱文：这些都是非常不同的体验。

阿卜杜斯-萨布尔：是的，它们是非常不同的体验。作为领域内的人来说，非常令人兴奋的是，如果你看30年前，例如，我们没有很多分子层面的参与者，甚至没有一个切入点来思考这是如何运作的。

我们对神经解剖通路有一个基本的认识。所以，你有这些外周感觉神经元，叫做，呃，它们起源于叫做背根神经节的结构。我们有大约30对这样的神经节沿着脊髓排列。它们向皮肤或其他内脏器官发送一根长突起，向脊髓发送一根突起。

从脊髓开始，另一组神经元接手传递，到达脑干，然后从脑底部到达大脑各处的其他区域。

所以，神经解剖通路，我们在相当长的时间里已经有了这些认识。但正如你提到的，有触觉，有热，有冷，有痒，这些是非常不同的。所以，特异性就体现在这里，它能让我们精细地检测这些不同的感觉。

而且你知道，我们这个领域在过去15、20年里经历了一场很好的革命，在这些外周神经系统的感觉神经元中，我们已经识别出了赋予特异性的受体蛋白。

其中两个最著名的例子我要提一下，因为它们是2021年诺贝尔奖的主题。一个是发现了一种叫做TRPV1的受体蛋白。瞬时受体电位香草酸亚型1。这是在大卫·朱利叶斯的实验室发现的，他着手确定辣椒，为什么我们会把它们感知为“热”的？我们对哪些神经元可能做到这一点有一些概念，但如何在分子层面解释“如何”呢？

于是他设计了一个非常巧妙的筛选实验，他将受体克隆到一个细胞系中，基本上就是施加辣椒素，即辣椒中的活性成分。他想找到那些一旦添加辣椒素就能产生细胞内反应的细胞。它们可以以钙离子进入细胞的形式被激活，这是神经活动的一个代理指标。

这种活动可以通过添加某种受体蛋白来实现。所以他进行了筛选，最终找到了这个我们现在称之为TRPV1的通道，当它在细胞表面表达时，赋予了细胞对辣椒素作出反应的能力。

我们现在知道，而且他们在那篇论文中证明了，同一个受体介导了对热量的反应。所以，这就是为什么辣椒素和辣椒会有这种热感，因为感知热量的神经元也对辣椒素作出反应，它们表达这种单一的蛋白质。

这篇论文发表大约在1999年，我相信。它真正开启了疼痛研究的分子时代，因为现在我们有了一个受体，我们可以说，好的，如果它表达这种TRPV1受体，这就是你定义疼痛神经元或热感知神经元的方式。

莱文：所以它们实际上是物理上特化的神经元。它们在物理上是不同的。

阿卜杜斯-萨布尔：它们与其他神经元在物理上是不同的，通过它们表达的基因和表面蛋白质的构成来区分。

现在，这是在上世纪90年代末，仅仅几年后，阿尔代姆·帕塔普蒂安的实验室进行了另一项开创性研究，他与大卫·朱利叶斯共同获得了2021年诺贝尔奖。他在另一个细胞系中进行了类似的筛选，寻找赋予机械感觉的受体蛋白。好的。在那里他们做了略有不同的筛选，他们使用RNAi来降低细胞系中受体蛋白的表达，他们知道这个细胞系是机械敏感的，并且可以表明如果没有这种或那两种蛋白质，细胞就不再对机械力作出反应。

我们现在称这些基因为Piezo1和Piezo2，在大多数情况下，几乎我们所知道的每一个对机械敏感的神经元，即可以将物理刺激能量转化为神经系统语言——电活动的神经元，都是由这种机械传感器Piezo赋予的。它不仅仅存在于神经元中；也存在于非神经元细胞中。

所以这是另一个例子。我刚给你举了两个感觉神经元的例子，但如果这个神经元有TRPV1，它会对热，有害的热作出反应。而如果这个神经元有Piezo，它会对压力作出反应。还有其他种类的受体赋予痒或冷等感觉。

现在作为领域，如果我跳到2026年，刚刚颁发了大脑奖，这是神经科学领域最大的奖项，又一次颁发给了我们领域的哈佛大学大卫·金蒂教授和欧洲的帕特里克·恩福斯教授。他们做了真正开创性的工作，表明至少有15种不同的疼痛、触觉、痒觉神经元类别，这些类别由它们表达的不同基因、它们的生理特性、它们在皮肤内的表达模式来定义。作为领域，我认为我们已经并且正在取得非常伟大的进展。

所以你知道，还有什么要做的，以及为什么我还有工作？你知道，我认为，作为领域，我们已经在外周检测方面学到了很多。真正驱使我在实验室工作中前进的事情之一，是在外周神经系统、皮肤中的所有这些机制，以及这与大脑中感知所在的位置之间建立联系，对吗？建立联系。这种身体、大脑、生理和信号传导。我认为这是这个领域下一波重大发现即将到来的地方。

莱文：那么这里的话题实际上已经从某种行为科学转向了真正硬核的分子和遗传科学。你的特别兴趣非常具体地集中在皮肤上，正如你所说的，我知道你已经量化了一个疼痛量表，试图有一种更定量的方式来讨论这些问题，而不是仅仅对行为进行定性观察。请告诉我关于疼痛量表以及这项工作是如何结合的。

阿卜杜斯-萨布尔：这是个很好的问题。你知道，这实际上有点像一次支线任务。所以，我在遗传学和分子生物学方面最为得心应手。正如我之前提到的，研究啮齿动物的疼痛是很有挑战性的。它们不能与我们交谈，对吧？我看到，为了让我在理解遗传和分子操作方面具有精确性，我必须后退一步，理解行为。而这后退的一步已经花了10多年，就像一直在埋头努力制作这些啮齿动物疼痛量表。

在我们的一些研究之前，领域内已有的只是，你用你认为痛苦的东西戳动物，如果它们做出反应，它们就在疼痛中。如果它们不反应，它们就没有疼痛。

疼痛是如此复杂，对吧？想想如果有人戳你一下，然后看你是否抬起了手，这足以解释你的疼痛状态吗？不。它丰富得多。所以，这就是我们试图用这个啮齿动物疼痛量表所做到的，给它们的感觉加上一个数字。

莱文：当然，医生会要求你给自己的疼痛打分，这太有意思了。这不是你能测量的东西。

阿卜杜斯-萨布尔：是的。这又涉及到另一个让我们在疼痛领域夜不能寐的问题：直到今天，2026年4月21日，我们仍然没有疼痛的生物标志物，对吧？这让我们抓狂。你无法进行石蕊测试。没有像“如果这个基因上调了”或“如果这个大脑区域活跃了”就意味着你在疼痛，如果没有，你就没有。

我们没有那个。我们在寻找。我们和领域中的每个人都在寻找，但我们还没有。在临床上，我们必须依赖自我报告。人们主要是告诉我们他们的感受。在fMRI和其他脑成像方法方面已经有一些进展，看起来很有前景，也许我们最终会有一天能有一个特征让我们自信地说某人处于疼痛状态而不是其他状态。但我们还没有做到。

莱文：嗯哼。作为一个动物爱好者，并且关注科学史上与动物关系的复杂性的人，您如何看待继续与动物合作的伦理问题？

阿卜杜斯-萨布尔：这是一个棘手的问题，你知道。我们有一个机构动物护理和使用委员会，我们对动物做的每一个实验都必须提出理由，对吧？我们必须使用最少数量的动物，并且尽最大努力诱导最少的疼痛来研究我们感兴趣的生物过程。

对于一个研究疼痛的人来说，这是一个挑战，因为我们必须诱导疼痛才能研究它，对吧？我认为我们的行为分析的一大好处是，因为我们现在获得了如此高的分辨率，我们可以用更少的动物来达到我们的统计观察和结论。所以，这有助于动物福利。

我们尽最大努力人道地、尊重地对待动物，因为我们确实明白它们通常在为人类的利益而献出生命。这是我们必须意识到的事情。我们需要药物，需要治疗方法，需要疗法。动物研究通常是这条管道的一部分。我在伦理上对此感到坦然。

我知道有些人并不这样认为。我不需要去说服人们改变他们的信仰或想法。我尊重那些观点。也有人说过，“我喜欢你做研究的方式，但从伦理上来说不适合我。”我也理解这些担忧。

但我认为，你知道，在2026年，我们仍然处于需要动物来了解疼痛系统如何运作以及如何设计安全的方法来缓解慢性疼痛的阶段。我们没有更好的模型来做这件事，所以我们必须负责任地、合乎伦理地使用这些动物模型。

那么，这会不会改变？会不会有一天我们可以使用计算机模型或模拟或类器官模型，学到与动物模型同样多的东西？也许那一天会到来，我们将不得不重新审视这个问题。也许不会有一天我们可以继续证明使用动物来研究疼痛或进行神经科学研究是合理的。但我认为那一天还没有到来，它们仍然是研究的重要途径。

莱文：那么，这就提出了一个问题，你在学术环境的实验室中进行的这些基础研究，如何转化为对人类患者的治疗？

阿卜杜斯-萨布尔：是的，我认为任何生物医学研究者的目标，比如我，我是基础科学家，好奇心驱动的科学家，我认为即使在做出发现时没有直接应用，为知识而增加知识也有巨大的价值。

然而，话虽如此，我确实相信我们有责任对公众和资助我们研究的纳税人负责，思考我们正在做的基础工作如何转化为疗法和治愈方法，特别是对于疼痛，对吧？有数以百万计的人患有慢性疼痛。

在啮齿动物中工作的美妙之处在于，我谈到的许多基因和分子、神经元通路都是高度保守的，对吧？疼痛系统的布线和神经解剖学在啮齿动物和人类之间是高度共享的，好吗？我们确实是在这样的前提下运作的：我们发现的一些东西可以直接应用。

我要提一个令人兴奋的例子。2000年代初期一些关于人类的研究表明，有一个家族的患者完全感受不到任何疼痛。纵观历史，有这些罕见的案例，有些人就是感觉不到任何疼痛。实际上，这并非好事，因为这些患者中的许多人活不长。他们实际上会伤害自己。你知道，从进化的角度来看，疼痛对我们的身体是有益的。

莱文：好的信息。

阿卜杜斯-萨布尔：这是好的信息。尤其是在发育过程中，你学会了不去碰那个热炉子，对吧？不去做可能伤害你的事情。

总之，在巴基斯坦有这样一个家庭，他们感觉不到任何疼痛，所以你可以进行遗传研究来追踪疼痛和敏感性。科学家们去那里做了真正英雄般的工作，他们测序了他们的DNA，发现他们都在一个单一基因上有突变。它叫做Nav1.7。这是一个电压门控钠通道，好吗？这个通道，这种蛋白质，似乎在周围神经系统的疼痛神经元中非常特异。如果人们没有一个功能性的这个蛋白质版本，他们就不会感到疼痛。

然后相反地，另一类患者的情况完全相反。这被称为“燃烧人综合征”，他们一生中主要在四肢有自发性疼痛。结果发现突变是在同一种蛋白质中。这种蛋白质，你没有它，就没有疼痛。太多了，就很多疼痛。

同样的事情发生在啮齿动物和我们研究过的许多其他哺乳动物身上。这种电压门控钠通道对于神经元传导动作电位的活动非常重要，特别是在疼痛神经元中。事实上，已经有一些被改进的新药实际上阻断了这个特定受体，似乎改善了许多患者的疼痛。

这种蛋白质的另一个版本叫做Nav1.8，似乎具有类似的功能。所以也许未来的一些疗法，我们会同时阻断这两种蛋白质。

而这项工作，其中很多是在啮齿动物中进行的。这里是一个例子，展示了动物研究和直接转化之间的来回和交叉对话。

我们实验室非常兴奋要做的事情之一，我提到了这些行为工具。利用我们的行为工具，我们可以在啮齿动物中区分疼痛的感觉成分和更情绪化的成分。因此，大脑中似乎确实存在一个情绪网络——如杏仁核、前扣带回皮层、岛叶皮层和其他一些区域，这些区域似乎赋予疼痛的情绪成分。这是如何运作的，你知道，我们和其他人都在努力工作。

但我想表达的观点是，回到你关于转化的问题。如果未来的疗法不是在外周神经系统层面、在感觉层面针对疼痛，而是在感知层面改变它，也许改变疼痛的负面情绪状态，那就太好了。因为也许我们不想要一个完全感觉不到疼痛的世界，正如我们提到的，疼痛确实有某种目的，对吧？

但是，如果我们能去除“痛苦”的部分，同时保持感觉的完整，那么也许这就是我们想要处理疼痛的方式。但我们必须深入了解这是如何运作的，才能有针对性。但我想象未来这是可能的。

莱文：太有趣了。我的意思是，我甚至不想知道他们是怎么发现这个家庭感觉不到疼痛的。我甚至不想知道他们发生了什么，才引起了科学界的注意。

阿卜杜斯-萨布尔：你知道，在一些国家有很多街头艺人会做这些事情——你知道，他们会在热煤上行走或做些什么。而且，你知道，那个家庭中的一个孩子，他会表演特技。他会爬上二楼的建筑然后跳下来，然后就立刻弹起来。每个人都会欢呼。所以诸如此类的事情。

莱文：在心理上克服疼痛或减轻疼痛的能力对我来说太迷人了，因为我们表现得好像心理是与身体分离的。但我们真正的意思是大脑中的神经元在做什么。而且我认为存在这种魔法思维的文化，认为我们可以超越疼痛，但在某种意义上有可能是生理上确实可行的。

阿卜杜斯-萨布尔：这是非常正确的。你谈到的也是我进入疼痛和疼痛研究的原因之一。有一本非常好的书叫《疼痛的挑战》，由梅尔扎克和沃尔撰写，他们是我们领域两位真正开创性的科学家，他们提出了疼痛历史上最重要的理论之一：疼痛的“闸门理论”。但总之，在这本书中，他们列举了所有这些案例，人们本应经历大量疼痛，但他们没有。你知道，有些人可以被催眠，然后他们的疼痛就消失了。

这样的事例太多了，不能认为这不是一个真实的现象。一个我们确实了解更多一点的相关现象，人们开始在小鼠中建模，我觉得这真的很酷，就是安慰剂效应，实际上对疼痛来说非常强大。

如果他们有一个强烈的期望和信念，认为这个东西会改变我的疼痛，它确实可以起作用。反过来，如果你告诉某人，“我要给你这种治疗，它对任何人都没有效果，每个人都说它很糟糕，但你也没有别的选择了，我只想无论如何试试看。”他们会回来说，“医生，你说得对。它没起作用。”而且可能是同一种药，对吧？

所以这种对疼痛缓解的期望和信念非常强大。我们现在知道它肯定利用了我们的内源性阿片系统，我们内在的控制疼痛的系统。它触及这些东西。如果你阻断阿片受体信号，你可以阻断许多这些效应。

这不是魔法，但它作用于大脑中确定的神经回路。有许多实验室在努力研究，格雷格·科德、马特·邦加特和格雷格·谢勒等人，试图绘制出这是如何运作的。

莱文：太神奇了。我确实看到你谈到过疼痛与成瘾的联系。特别是与阿片类药物有关的。

阿卜杜斯-萨布尔：对。

莱文：而你说的是，疼痛和成瘾之间存在联系是有生物学基础原因的。

阿卜杜斯-萨布尔：是的，这是非常正确的。我们有一个内源性阿片系统，可以被许多事物激活，我们全身到处都有这些阿片受体。

我的意思是，阿片受体的发现可以追溯到上世纪70年代末，在啮齿动物中，他们可以刺激大脑中的一个区域，即中脑导水管周围灰质。你可以得到非常强烈的疼痛缓解。老鼠的尾巴会放在热板上，你刺激大脑中的这个区域。然后它们就不反应了，好吗？他们发现这个区域充满了阿片受体。这种反应依赖于内源性阿片系统的激活。

阿片类药物可以是强大的疼痛缓解剂，而且受体无处不在。这就是为什么它们也有这么多不良副作用的原因，因为它们作用于疼痛系统，但它们在周围起作用，它们在膀胱、肠道、背根神经节神经元、脊髓中起作用。它们遍布各处，所以它们带来了除疼痛缓解之外的许多不良副作用。

[音乐播放]

斯特罗加茨：哇。那里有这么多令人惊讶且非常直接的事情值得思考。我认为任何收听这期节目的人都能有所共鸣。

莱文：嗯哼。我之前并没有真正意识到阿片类药物……当然，我猜我知道它们是止痛药。我知道那是常识。人们最初是为了寻求疼痛缓解，但我以为那是一个外部结果，你知道吗？我没有想到它是针对同样的生物机制。

这真的让我很惊讶，而且我们有这种内源性的、自然的机制可以做同样的事情，这就是为什么它表明我们可以在某种程度上在心理上克服疼痛，你知道吗？我想这也照亮了一些东西。我们对我们的思想和身体如何运作还有很多不理解的地方。

斯特罗加茨：我相信。看任何魔术，你都会明白这一点。但不，我的意思是，在像疼痛这样物质性的东西中，我的意思是，对吧？那不是幻觉。然而，也许它的某些方面是幻觉。这很令人困惑。

莱文：是的，我不确定那是幻觉。我的意思是，事情是被触发的。有信号，对吧？但你可以用其他化学物质淹没受体。我的意思是，这对我来说听起来就是这样。而且它有一个有趣的进化角色，对吧，疼痛在生存方面。重要的是，如果你的脚骨折了，我们不会跑去活动，而没有疼痛受体对生存是非常不利的，他们知道有些特定的人感觉不到疼痛。所以，当你的背在水槽边疼的时候，就感激它吧，史蒂夫。

斯特罗加茨：是的，我明白了。我应该为我的疼痛受体感到感激。

莱文：完全正确。好了，休息之后，我们要把疼痛抛在脑后，我们要谈论一些更愉快的事情，那就是奇妙的裸鼹鼠。

[音乐播放]

莱文：欢迎回到《为什么的乐趣》。我们正在与神经科学家伊斯梅尔·阿卜杜斯-萨布尔交谈，他研究大脑和我们的触觉。

我确实想转向你在疼痛对立面方面的重要工作，即关于轻柔触摸、社交触摸和愉悦触摸。所以，我既好奇是什么吸引你转向这个方向，当然也想知道参与轻柔触摸或抚摸触摸的受体与疼痛受体有何不同，以及为什么这在动物和人类可能的社交结构中如此重要。

阿卜杜斯-萨布尔：好问题。你知道，当我即将结束在宾夕法尼亚大学的博士后研究，大约八年前开设我的实验室时，我开始思考，好吧，谁会愿意来我的研究实验室工作呢？如果我只有研究疼痛的项目，也许那会让人望而却步。也许有些人会更愿意研究，你知道，社交触摸、令人愉悦的、好的东西。事实就是这样，是的。

我要向我的同事致敬，加州理工学院的戴维·安德森。他发表了一篇我作为博士后读到的论文，它非常引人入胜和令人兴奋，因为他们发现有一群神经元似乎被老鼠皮肤上的抚摸触摸激活，与这些是愉悦社交触摸检测器的特征一致。

而那篇论文，他们没有研究大脑，也没有将其与任何行为联系起来。所以我认为这很适合我这个有遗传学和分子操作背景的人，进行非常仔细的行为分析，并与脑成像联系起来。所以，这些神经元和这个通路与疼痛的区别在于它是一个不同的分子群体。这些神经元恰好表达一种基因，至少在小鼠中，叫做MRGPRB4。这是个绕口令。它们确实表达Piezo通道，我告诉过你的另一种重要的机械传感器。所以，它们肯定是机械感觉神经元。

使它们特别的是它们表达的一组基因，这与介导其他类型躯体感觉的其他类别不同。它们的布线，它们支配通常被触摸的毛发皮肤区域。它们在脊髓中连接的神经元，以及从脊髓到大脑的神经元。基本上，从皮肤到大脑的整个通路将与热、冷或疼痛的通路不同，好吗。所以，整个电路，解剖结构，布线是完全不同的。

莱文：哇。所以又是高度特化的。

阿卜杜斯-萨布尔：再次高度特化。例如，如果你刺激动物的疼痛通路，它们很快就会给你信号表明这是痛苦的，它们不喜欢它，它们会避开它。但是对于这个通路，它们给我们信号表明它们实际上喜欢它。它们想花时间在被刺激这个通路的环境中。如果我们观察例如大脑奖赏中心的多巴胺释放，我们可以看到刺激皮肤中的这个通路会导致这种多巴胺释放，或者如果我们基因上消融了这些神经元，我们会看到社交触摸行为大大减弱。

现在，我们正在进行的一些研究让我们非常兴奋，因为这又回到了你的问题，关于为什么它在人类中重要和具有转化影响。你知道，我们认为这个通路对于触摸缓解压力、焦虑和抑郁的能力也很重要。

当你情绪低落或经历负面情绪时，想想来自亲人、父母、朋友的拥抱。它确实能让你平静下来，让你感觉更好。我们理解这个现象，但它在分子、细胞和神经元水平上如何运作几乎完全未知。我们发现和阐明的社交触摸的皮肤到大脑通路，我们认为可能对此很重要。我们有非常强的证据。虽然尚未发表，但希望，你知道，也许今年晚些时候我们会提交这篇论文，表明激活这个通路可以缓解负面状态，这真的很令人兴奋。而且我们确实认为它具有直接的转化潜力。也许我们甚至可以考虑治疗大脑疾病、慢性压力，不是在大脑层面，而是通过靶向皮肤中的神经元。

莱文：哇。太迷人了。现在有你做过的这样一项研究，你通过基因改造让小鼠对蓝光敏感，这样你就不是实际地抚摸它们，而是用蓝光照射它们，它们就能体验到被轻柔触摸的感觉。所以，我对这个问题有很多方面。

一个是，这样做真是太疯狂了。这不是一个问句。另一个是，你知道，我们是否会基因改造人类，让他们可以进行蓝光疗法，作为某种，你知道，治愈某些精神障碍的尝试？

阿卜杜斯-萨布尔：是的，如果有一天我们能实现，那就太好了。这项技术被称为光遗传学，我认为它是整个神经科学中最重要的技术之一。希望我们的同事能因此获得诺贝尔奖。

但总之，这展示了进化生物学的美妙之处，以及跨物种观察，有一种蛋白质在藻类中，可以让藻类在泥泞的池塘中向蓝光推进。它是一个离子通道，一个非选择性阳离子通道，基本上就是说蛋白质的一部分在蓝光照射时，通道打开，允许正离子涌入表达这种蛋白质的细胞。

这对神经元来说非常完美。神经元是电可兴奋的细胞，通过正离子电流流入神经元来放电。所以，如果你能通过某种病毒基因工程把这个特殊蛋白质放在你的神经元表面，你就能赋予直接激活这些神经元的能力。

所以，在这个项目的一部分中，我们进行了一些基因工程，将小鼠杂交在一起，把这个蓝光敏感蛋白只放在这些神经元中。我们可以直接照射皮肤，正如你所说，来引发行为。

现在，要在人类中做到这一点，必须达到能够通过基因工程将这种蛋白质添加到感兴趣的细胞类型的程度。

人们现在正在做这件事来治疗——这不是我们的工作——但实际上是在治疗某些形式的视网膜变性和失明。这真的很不可思议。所以也许有一条使用这项技术治疗人类疾病的途径。

莱文：你谈到了在小鼠和人类中某些复杂系统中某些神经网络的相似性。但你以其对裸鼹鼠的研究而闻名，谁不喜欢一个伟大的裸鼹鼠群体呢？请，为那些不了解非凡的裸鼹鼠的人，你能为我们描述一下它们吗，以及为什么它们的群体在啮齿动物王国中如此不寻常？

阿卜杜斯-萨布尔：是的，它们是我见过的最迷人的动物之一。有些日子我们会想，“我们到底在研究什么？”有些日子我们真的就坐在那里盯着它们看。

莱文：观察它们？

阿卜杜斯-萨布尔：是的，是的，是的。因为它们的生物学太迷人了，但有一些事情让我们非常兴奋。

首先，它们感觉不到许多形式的疼痛，原因尚不完全清楚。它们似乎对癌症免疫或具有抵抗性，无法患癌症。它们作为啮齿动物来说寿命很长，它们能活大约30到40年。

莱文：哇，这对啮齿动物来说真是长寿。

阿卜杜斯-萨布尔：是的，是的。大多数小鼠和大鼠只活一到两年。是的。是的。而且它们没有传统意义上的衰老迹象。所以，当它们死去时，它们就是死了。你无法通过观察来判断它们的年龄。它们似乎没有任何认知或身体衰退。它们就是死了。

而且它们高度社会化。这是我们实验室迄今为止真正关注的一点。在过去三年多的时间里，我们一直在与它们合作。它们实际上是整个哺乳动物王国中最具社会性的动物。一个群体可以包含几十只到几百只动物，它们都生活在一起，是一个联系非常紧密的群体。它们由一个单一的雌性蚁后主导，她是母系首领，引导整个社会。所有其他动物基本上都是工蚁和雄蜂，在蚁后面前生殖受到抑制。她是唯一与群体中一两只繁殖雄鼠交配的个体。她一生都在持续生育。所以，没有更年期或放慢脚步的迹象。所以，当她生产一窝幼崽时，它们永远不会离开。群体只是越来越大、越来越大，好吗。它们决定了为了整个群体的生存，最好一切都要一起做，好吗。

它们主要来自东非、肯尼亚、埃塞俄比亚。它们完全生活在地下。主要的假设是，你知道，也许在这个干燥、干旱的沙漠气候中，食物和资源不丰富，更容易采用群居的生活方式，

英文来源：

How Does Touch Lead To Pain Or Pleasure?
Introduction
Pain and pleasure seem like simple facts of life, however they are anything but that. Neuroscientists still cannot say why physical pain differs from psychological pain, for instance, or why a loved one’s touch soothes while a stranger’s touch repels.
To explore the science behind these sensations, Janna Levin talked to Ishmail Abdus-Saboor, a neuroscientist at Columbia University’s Zuckerman Institute. Their conversation covers how pain serves an evolutionary purpose, how researchers measure pain and pleasure in the lab despite the absence of any objective biomarker, and how touch functions as a social and emotional signal, not just a sensory one. Abdus-Saboor also describes his work with naked mole rats — a species that barely feels pain, shows no signs of aging, and lives in colonies built almost entirely on touch — and the ethical trade-offs when studying sensations in animals that cannot describe what they feel.
Listen on Apple Podcasts, Spotify, TuneIn or your favorite podcasting app, or you can stream it from Quanta.
Transcript
[Music plays]
JANNA LEVIN: Hello. Hello out there, I’m Janna Levin.
STEVE STROGATZ: And I’m Steve Strogatz.
LEVIN: And this is The Joy of Why.
STROGATZ: A podcast from Quanta Magazine in which we explore some of the biggest unanswered questions in math and science today.
LEVIN: So Steve, we’ve been talking with Ishmail Abdus-Saboor who’s a professor here at Columbia [University], not a few blocks from me, about skin as an organ and as a vehicle for transmitting both pleasure and pain.
STROGATZ: Mm-hmm. That sounds very interesting.
LEVIN: Yeah. I think it’s interesting that very little is known about pain. I mean, if you think about your own experience, it’s kind of strange when you start to meditate on it. What is it exactly, right? It’s very unpleasant, but other than that, what is it?
STROGATZ: It’s really mysterious, especially when you have pain that doesn’t really relate to tissue damage. Like, sometimes I’ll just be washing something at the sink in the kitchen, and then suddenly I have pain, and I think, “Come on, that’s ridiculous. I didn’t do anything to my back.” And, you know, people will tell you pain is mental. You can sort of talk yourself out of certain pain, which raises the point that pain is not as simple as it might seem at first.
LEVIN: Yeah, and in particular, he studies this at the level of animals. But it’s one of these things that’s very hard for animals to tell you reliably what they’re experiencing. So, a lot of his work is really trying to interpret the animal’s interiority, the animal’s experience of different sensations.
STROGATZ: Yeah, I wondered as you were describing this work, is it touch as a means to learn about interiority, or is touch the primary object of interest here?
LEVIN: I mean, I think that that’s an interesting question. Like, with many scientific ambitions, sure, maybe the big goal is consciousness, right? But no, the big goal is always very far off. That’s not the language in which they’re operating.
The language in which they’re operating is data, observations. You know, it’s more immediate to their experiments.
STROGATZ: Well, right. They say science is the art of the solvable, and so we’re trying to restrict ourselves to things where we can make advances, make real progress.
But I have to say, I got a little bit of a queasy feeling when you mentioned pleasure and pain, especially as a person with an animal at home. My dog, Murray, that I love so much.
LEVIN: Yes, I’ve heard about Murray.
STROGATZ: I know. I’m sure everyone has.
LEVIN: I’ve seen pictures of Murray.
STROGATZ: Okay. Okay. But still, I mean, the thought of pain, you know, and I know there’s a lot of animal rights people among our listeners. So I hope in listening to this episode, I don’t know, what’s the pain part of this gonna be about?
LEVIN: We did talk about this. I mean, this is a very gentle animal lover. It’s really interesting to talk to Ishmail. His experiments, they’re gentle. Maybe, they’ll notice if a paw is retracted, so if it’s uncomfortable, but they’re not torturing these animals.
But even then, I think animal experimentation, even in the most benign sense, is called into question. And he thinks about the ethics of that.
Well, let me introduce our guest. His name is Ishmail Abdus-Saboor. He’s a neuroscientist just down the road at Columbia University Zuckerman Institute, and he studies the skin-brain axis, and in particular, our sense of touch, including gentle touch and soothing touch.
STROGATZ: Fantastic.
[Music plays]
LEVIN: Welcome to The Joy of Why, Ishmail. I’m so glad to speak to you.
ISHMAIL ABDUS-SABOOR: It’s an honor to be here with you as well.
LEVIN: It is a pleasure to get to know colleagues on the same larger campus. I’m very interested in starting with your journey. You grew up in Philadelphia. I read some of your other interviews where you discussed your love of animals, and how at one point you converted the third floor of your home into a year-long science experiment. And maybe I’m exaggerating, but tell me about your initial relationship with animals as a child.
ABDUS-SABOOR: Yeah. Yeah, it’s really joy to be here and, I think, if you were to ask me when I was a kid, what I wanted to do with my life and career, I always said I wanted to become a scientist. You know, I didn’t know any scientists directly, but if I thought about the classes in school, that kept me very excited and energized, and I would watch Animal Planet a lot as a kid and I could just watch nature shows for hours on end.
I had many pets growing up, dogs and cats, but also like lizards and turtles and snakes. You know, I remember, like, as a kid having this subscription to this, like, Turtle Digest sort of a magazine. You know, I was very fascinated about biology and biological systems and how animals communicate and cooperate. I think my science career set in motion in earnest as a freshman in high school, as you alluded to, at Central High School in Philadelphia, as a part of an honors biology class. You know, actually, we didn’t get gym class because to sign up for this honors biology, we had to take two periods of biology. And for me, even as a 14-year-old kid, like, I just jumped at that opportunity. You know, who needs gym? Got teased a little bit.
But, you know, as part of that project, we were able to do this year-long science fair project, and many of the students worked at neighboring universities in Philadelphia, Temple or Drexel, or UPenn. But we also were able to do science at home. So this is what I did. You know, basic rudimentary equipment and things. And the project was actually looking at regeneration in crayfish.
So you know, my parents were very supportive of me and let me take over, you know, the third floor of our house there in the Germantown section of Philly. And, you know, there were hundreds of crayfish and I’m sure it didn’t smell so well up there. But at the time, you know, there was this really big push on, like, supplements and ginseng. And like ginseng was supposed to be like this magical supplement that, like, improved health and memory and all sorts of wonderful things.
So my idea was if I spiked the crayfish, their water with this ginseng herbal supplement, then this could, like, speed up the rate of regeneration because they do have the ability to regenerate lost appendages. So, you know, I got to become a scientist and I, like, trim parts of their appendages and measure the rates of it growing back. And, it was a very exciting time to keep a lab notebook and have hypotheses that I could test and to make graphs and plot my data and do statistical tests to see if there was anything here.
Unfortunately, I don’t quite remember the outcome of those.
LEVIN: You weren’t as diligent with your data analysis as you are now.
ABDUS-SABOOR: Yes, exactly. That’s exactly it.
LEVIN: We actually have something in common. My daughter is obsessed with animals, and at one point we had something like 23 animals in my New York City apartment. It looked like a Petco. There were snakes, lizards, tarantulas. It was insane. Only one time did one animal kill another animal. It’s a real calling, I feel, this interest in animals.
But you ended up studying smaller-scale biology, cellular, molecular. What led you to make that transition from this sort of love of animals to the actual smaller-level biology?
ABDUS-SABOOR: When I went to college, I thought, you know, again, this love of animals, maybe I wanna become a veterinarian.
So I worked in a number of veterinary clinics and hospitals, and there my experience was, like, helping the vet with spaying and neutering and, and it was very monotonous and, and frankly, quite boring. And I kinda missed, like, this kinda fast-paced nature of biological exploration. So I did another internship my junior year in college at University of Pennsylvania in the Cell and Developmental Biology department, and there we were working on, you know, cells in the hearts of mice, uh, um, proteins in the hearts of mice that are important for cardiac development and function.
And there I got exposed to molecular biology research and working at the bench, and just the culture of science, the whole ethos of the, you know, of scientific discipline at lab meetings and people presenting results and, and just talking about all the open questions and, and being able to, to look at life at the scale of molecules, DNA, RNA, you know, the molecules of life.
I thought that was just very exciting. It wasn’t until a few years later that I moved into, like, neuroscience and sensory neuroscience.
LEVIN: Yeah. There’s this interesting history, painful history — pardon the pun — of our relationship with animals and, sort of denial of the idea that animals are conscious or that they feel pain.
ABDUS-SABOOR: Yes.
LEVIN: Uh, and so going back to Descartes in the 17th century, he infamously performed vivisections when, you know, live animals howling. How could he possibly — and I’m not actually asking you to defend this point of view — but how could he possibly have suggested that the animals were not feeling pain?
What’s your understanding of how we transition from this physical detachment, you know, as our colleague of ours at Quanta said, “They don’t think, therefore they are not.” That was his attitude to accepting that animals feel pain.
ABDUS-SABOOR: This is a wonderful question, and it’s one that I’ve thought a lot about and keeps me and everyone in the lab awake at night. I mean, it’s a part of a broader question, the question of consciousness, right? Do animals have a level of consciousness that we would have?
So if we boil this down to the idea of pain and how it works and where do we draw the line on whether or not animals feel pain? It’s a debate that has raged for many years and I think the modern idea is that you need a brain, you need some central processing unit to have full function and cognition to be able to experience pain.
If you look at lower animals, perhaps, no one denies that they can sense nociception. Nociception, it’s a fancy term for receptors, neurons, out in the peripheral nervous system that can be activated by noxious stimuli. And those signals travel to some central processing units so that the animal knows to like move away. And I think this idea, everyone appreciates. Even simple, you know, bacteria, right, single cell organisms if you put them in an environment that’s not conducive, they’ll move away. They’ll recoil, because they have sensory neurons out in their peripheral nervous system.
Now, we would consider that nociception, but not quite pain. Encapsulate the experience of pain, you have to have a central processing unit whereby you can respond appropriately to subsequent noxious stimuli. There’s some sort of learning and memory. There’s higher level cognition. You understand that this particular stimulus that I’ve received, like, causes me pain, so now I’m going to avoid it.
So then the debate is, if that’s the case, then which animals have it and which animals do not? And I think, as a neuroscience community, by and large the idea has been that many animals, especially lower animals, perhaps do not have that level of higher cognition and consciousness.
You know, a question I get all the time, right, people, especially in the New England area, they ask about lobsters, right? Should I feel bad about throwing this lobster in this hot boiling pot while it’s still alive?
LEVIN: The classic example of slow boiling the lobster.
ABDUS-SABOOR: Exactly, but then people say, “Well, they tell me they can’t feel any pain, so I shouldn’t feel bad.” And they ask me, “Is that true?” Depends on who you ask, right? And perhaps you have to do the test.
So as a field, like the classical test that we do is like this conditioned place aversion. So does an animal have enough brain real estate to understand that this thing is noxious? They should be able to understand that the environment that they received this noxious stimulus is bad. Such that if you put them in that environment later, they can remember that something I received here was not good and I want to escape or avoid it.
Animals that don’t have that cognitive ability, even though they’ll recoil from something noxious. They don’t have the ability to form the memory, a conscious perception, the negative feeling that is attributed to pain, right?
So this is what people do, and if you can do this test and show that they can make these associations, then people say, “You know what? I think this animal can feel pain, and let’s add that animal to the list.”
LEVIN: This is interesting because the animals you work with specifically have to feel pain to be part of your study but also don’t. And that’s also part of your study. Why they don’t—we’ll come to the naked mole rats.
ABDUS-SABOOR: Yes. We mainly work with rodents, and I think it is accepted that rodents can experience pain or nociception. They will withdraw their paws, like we would withdraw our hands. There is some debate in our field about, again, these higher-level components of pain, the emotional negative valence that’s associated with pain. How much of that are rodents experiencing?
And this is part of, like, I think the importance of some of my work because we’ve taken really detailed behavioral mapping of animals as they experience different stimuli. And we can say actually they respond in ways that they can’t describe to us their ongoing emotional states, but if we can use behavior as a readout of their internal states, they are displaying behaviors very characteristic of negative emotional states of pain and we’re trying to, like, kind of map that in the brain.
LEVIN: It’s a very interesting question that you’re raising because while reading about your work, I was wondering about the ways in which psychological pain differs from physical pain. And beyond differing, how they’re interconnected, right? As you’re describing, if the animal doesn’t have the psychological component, we downgrade it in terms of severity.
ABDUS-SABOOR: That is very true. And you know, I think many times we downplay animal intelligence or cognition because we don’t know how to tap into it. We haven’t designed the right test.
You reminded me of some work from a colleague of mine, Professor Kay Tye at University of California San Diego and also the Salk Institute. In rodents, she’s asking this question, physical pain and emotional, psychological pain do they map or intersect anywhere in the brain? And she designed a really clever test, which she calls the FOMO task in mice, the fear of missing out, where she’ll have mice that are living together. And she puts a divider between them and the animal outside of the divider has to sit there and watch its friends get, like, this chocolate milkshake.
Okay, so the mouse is just watching its friends. The mouse is a little bit hungry, a little bit thirsty, and watching his friends take this milkshake. And her idea is that this is like a psychological form of pain. And then she’s doing recordings in the part of the brain called the insular cortex and asking the question like, does this interact with physical pain? And it appears that it does. Like it alters their threshold to respond to, like, physical pain after going through this emotional psychological pain. And maybe that there’s similar constructs in the brain, and we can even study this in a rodent.
LEVIN: Let’s discuss a little bit of the actual science that goes into this. So, your research in the somatosensory system deals with pain and touch and skin. Can you tell me about some of the brain pathways and the different receptors involved in the different types of sensations?
ABDUS-SABOOR: Sure. So right, as you mentioned, the somatosensory system is our sensory system that mediates touch, pain, itch, temperature, pressure.
LEVIN: And these are all very distinct experiences.
ABDUS-SABOOR: Yes, they are very distinct experiences. Really excitingly for us as a field, if you would look 30 years ago, for example, we didn’t have a lot of the molecular players to even have an entry point into thinking about how does this work.
We had a basic idea of the neuroanatomical pathways. So, you have these peripheral sensory neurons called, uh, they emanate from a structure called the dorsal root ganglia. And we have, like, 30 pairs of these that run alongside our spinal cord. They send one long process to the skin or other internal organs and one process to the spinal cord.
From the spinal cord, a different set of neurons kind of picks up the relay, goes to the brainstem, and then from the base of the brain to other areas throughout the brain.
So, the neuroanatomical pathways, we kind of have had this for quite some time. But as you mentioned, there’s touch, there’s hot, there’s cold, there’s itch, like these are quite distinct. So, it’s where the specificity resides that allows us to exquisitely detect these different sensations.
And you know, our field has had a really nice revolution in the last 15, 20 years where within these sensory neurons out in the peripheral nervous system, we have identified receptor proteins that confer specificity.
And two of the most famous ones I’ll just mention because they were the subject of a Nobel prize in 2021. So, one was the discovery of a receptor protein called, um, TRPV1. Transient Receptor Potential Vanilloid 1. This was discovered in the lab of David Julius, who’s set out to determine, like, how chili peppers, like why do we perceive them as hot? We had an idea of which neurons may do it, but like, how do you explain the “how” at a molecular level?
And so, he designed a really ingenious screen where he cloned receptors into a cell line and basically applied capsaicin, the active ingredient in chili peppers. And he wanted to find cells whereby once you add capsaicin, there can be like an intracellular response. They can be activated in the form of calcium entry into the cell, which is a proxy for, like, neuroactivity.
And this activity can be conferred by adding a certain receptor protein. So, he screened and basically found this channel that we now call TRPV1, that when it’s expressed on the surface of cells, confers the ability to respond to capsaicin.
We now know, and they showed in that paper, that this same receptor mediates the response to heat. So, this is why, like, capsaicin and chili peppers have this heat sensation because the heat sensing neurons that also respond to capsaicin expressed this one protein.
This paper came out like in 1999, I believe. And it really began a molecular age of pain research because now we had a receptor that we can say, okay, this is how you define a pain neuron or a heat sensing neuron if it expresses this TRPV1 receptor.
LEVIN: So, they’re actually physically specialized neurons. They’re physically different.
ABDUS-SABOOR: They’re physically different than other neurons, by their constitution of the genes and the proteins they express on their surface.
Now, this was in the late 1990s, and there was another pioneering study just a few years later by Ardem Patapoutian’s Lab, who was the co-winner with David Julius on that 2021 Nobel Prize. He did a similar sort of a screen in a different cell line looking for receptor proteins that confer mechanical sensation. Okay. And there they did a slightly different screen where they use RNAi to knock down the expression of receptor proteins in the cell line that they knew was mechanosensitive and could show that without this one protein or two proteins, then the cells no longer responded to mechanical force.
We now call those genes Piezo1 and Piezo2, and for the most part, almost every neuron that we know of that is mechanically sensitive, meaning can convert physical stimulus energy into the language of the nervous system, electrical activity. It’s conferred by this mechanical sensor Piezo. And it’s not just in neurons; it’s in non-neuronal cells.
So here’s another example. I just gave you two examples of they’re sensory neurons, but if this one has TRPV1, it’s gonna respond to heat, noxious heat. And if this one has Piezo, it’s gonna respond to pressure. And there are other sorts of receptors that confer itch or cold, et cetera.
Now as a field, if I jump ahead to 2026, there was just The Brain Prize, which is the biggest prize in neuroscience, was just awarded in our field again to David Ginty at Harvard and Professor Patrik Ernfors in Europe. They’ve done really pioneering work to show there are at least 15 different classes of these pain, touch, itch neurons that are defined by their expression of different genes, their physiological properties, their expression patterns within the skin. As a field, I think we’ve made, and are making, really great progress.
So you know, what’s left to do, and why am I still employed? You know, I think, as a field, we’ve learned a lot about detection in the periphery. One of the things that really drives me in the work we do in my lab is making a connection between the peripheral nervous system, all these mechanisms in the skin, and how does this connect to the brain where perception resides, right? Making the connection. This body, brain, physiology, and signaling. This is where I think the next wave of major discoveries we’re ripe for in this field.
LEVIN: So here the subject really has shifted from a kind of behavioral science to really hardcore molecular and genetic science. Your particular interest is very specifically skin, as you’re saying, and I know that you’ve quantified a pain scale to try to have a more quantitative way of discussing these things as opposed to just qualitative observations of behavior. Tell me about the pain scale and how that work ties in.
ABDUS-SABOOR: That’s a wonderful question. You know, it was like a side quest actually. So, I’m most at home in genetics and molecular biology. As I mentioned before, studying pain and rodents is challenging. They can’t talk to us, right? And I saw that for me to, like, have precision and understanding the genetic and molecular manipulations, I had to take a step backwards and understand the behavior. And that step backwards has been like 10 plus years of this, like plugging away of trying to make these rodent pain scales.
What we had in the field before some of our studies was just like, you poke an animal with something that you think is painful, and if they respond, they’re in pain. If they don’t, they’re not in pain.
Pain is so complex, right? Just think if someone, like, poked you and looked at whether you lifted your hand, would that be sufficient to explain your pain state? No. It’s so much richer. So, this is what we attempted to do with this rodent pain scale to put a number on their sensation.
LEVIN: Which, of course, doctors ask you to rate your pain scale, which is so fascinating. It’s not something you can measure.
ABDUS-SABOOR: Yes. That gets to another point that keeps us awake in the pain field is that we do not, to this day, you know, April 21, 2026, we do not have a biomarker for pain, alright? This drives us crazy. You cannot get a litmus test. There’s no, like, if this gene is up or if this brain area is on, that means you’re in pain. And if not, you don’t.
We don’t have that. We’re searching. We and everyone in the field is searching, but we don’t have it. In the clinic, we have to rely on self-reports. People largely telling us how they feel. There have been some advances in, like, fMRI and other brain-imaging approaches that looks promising, and maybe we will get to a day where there’s a signature that we can confidently say someone is in pain and not some other state. But we don’t have that yet.
LEVIN: Mm-hmm. As an animal lover and a person who has looked at the complex history of science in relationship to animals, how do you reckon with the ethics of continuing to work with animals?
ABDUS-SABOOR: It’s a tough question, you know. We have an institutional animal care and use committee that every single experiment we do with animals we have to justify, right? And we have to use the lowest amount of animals and do our best to induce the least amount of pain to study the biological process we’re interested in.
It’s a challenge for someone who’s studying pain because we have to like induce the pain to be able to study it, right? One of the benefits I think of our behavioral assays is that because we now get so much resolution, we can test less animals to reach our statistical observations and conclusions. So, this kind of helps with animal welfare.
We try our best to treat the animals humanely and with respect because we do understand that they are giving their lives oftentimes for human benefit. And this is just something that we have to appreciate. We need medicines, we need cures, we need treatments. And oftentimes animal research is a part of that pipeline. And I’m comfortable ethically with that understanding.
Now I know there’s some people who are not. And it’s not upon me to convince people to change their beliefs or thoughts. I respect those. And there have been people who say, “I love the research you do, but ethically this is not for me.” I understand those concerns as well.
But I think, you know, in 2026, we’re still at a point where we need animals to learn how the pain system works and how to design safe ways to relieve chronic pain. And we don’t have better models to do this, so we have to work responsibly and ethically in these animal models.
Now, will that change? Will there be a time where we can use computer models or stimulations or organoid models and learn just as much as we can in animal models? Maybe that day will come and we’ll have to revisit this. Maybe there won’t be a day where we can continue to justify using animals to study pain or in neuroscience research. But I don’t think that day has arrived and they’re still very important conduits to study.
LEVIN: Well, this opens up the question about this fundamental research that you’re doing in a laboratory in an academic setting, how does this transition to therapeutic treatments for human patients?
ABDUS-SABOOR: Yeah, I think the goal of any biomedical researcher such as myself where I’m a basic scientist, curiosity-driven scientist, and I think there is major value in this increasing knowledge for knowledge’s sake, even if it doesn’t have a direct application at the moment that we’ve made the discoveries.
However, in saying that, I do believe we have duty to the public and the taxpayers who fund our research to think about how the basic work we’re doing can translate into therapies and cures and especially for pain, right? There are millions of people who suffer with chronic pain.
The beauty of working in rodents is that many of the genes and molecules, the neuronal pathways I’ve talked about are highly conserved, right? The wiring and the neuroanatomy of the pain system is very much shared between rodents and humans, okay? We really do operate under the space that some of the things we discover can have direct application.
I’ll just mention an exciting example. Some papers in the early 2000s in humans showed that there was a family of patients who can’t feel any pain whatsoever. And there have been these rare cases throughout history of people who just don’t feel any pain. It’s actually, like, not a good thing because many of these patients don’t live long lives. They actually injure themselves. You know, pain is, from an evolutionary perspective, good for our bodies.
LEVIN: Good information.
ABDUS-SABOOR: It’s good information. And especially during development, you learn, like, to not touch that hot stove, right? To not do things that could hurt you.
Anyway, there was a family of people in Pakistan who didn’t feel any pain, so you could do genetic studies and kind of trace the pain and sensitivity. And the scientists went over there and did really heroic work where they sequenced their DNA and they found they all had mutations in a single gene. It’s called Nav1.7. It’s a voltage-gated sodium channel, okay? This channel, this protein, seems to be very specific to pain neurons in the periphery. So if people don’t have a functional version of this protein, they won’t feel pain.
And then conversely, there’s another class of patients that have the exact opposite. It’s called, like, Burning Man syndrome, where they just have spontaneous pain, mainly in their extremities throughout life. It turns out the mutation is in the same protein. This one protein, you don’t have it, no pain. Too much of it, lots of pain.
Same thing happens in rodents and many other mammals we’ve studied. This voltage gated sodium channel is very important for the activity of the neuron propagating an action potential and specifically in pain neurons. And in fact, they’re new drugs that have been improved that actually block this particular receptor and it seems to improve pain for many patients.
There’s another version of this protein called Nav1.8 that seems to have similar functions. So maybe some of the therapies in the future, we’ll kind of do a double block of both of these proteins.
And this work, a lot of it is going on in rodents, Here’s a one example of a lot of like back and forth and crosstalk between animal studies and actually direct translation.
One of the things we’re very excited about doing in my lab, I mentioned these behavioral tools. And with our behavioral tools we can delineate in rodents the sensory component of pain versus more emotional components of pain. And so there does appear to be an emotional network in the brain — areas like the amygdala, the anterior cingulate cortex, insular cortex, and some other areas that seem to confer an emotional component of pain. How that works, you know, we and others are hard at work.
But the point I wanna make, back to your question about translation. It would be very nice if we could have therapies of the future that don’t target the pain at the level of the peripheral nervous system, at the level of sensation, but alter it at the level of perception and maybe alter the negative emotional state of pain. Because maybe you don’t want a world where you can’t feel any pain, as we mentioned, it does serve some purpose, right?
But, if we can remove the hurting component but keep the sensory intact, then maybe this is how we want to tackle pain. But we have to know how that works at a deep level to be able to kind of target that. But I can envision a future where that’s possible.
LEVIN: It’s so interesting. I mean, I don’t even wanna know how they discovered that this family felt no pain. I don’t even wanna know what happened to them that brought that to the scientific community.
ABDUS-SABOOR: You know, in some countries there are a number of street performers actually who do things – you know, they’ll walk on hot coals or like, do things. And, you know, one of the kids in that family, he would do tricks. He would climb the second-floor building and jump off and just pop right up. And everyone would cheer. And so these sorts of things.
LEVIN: The ability psychologically to overcome pain or to mitigate pain is so fascinating to me because of course, we act like psychological is disconnected from the body. But what we really mean is what the neurons are doing in the brain. And I think that there is this kind of culture of magical thinking that we can transcend pain but there might be a sense in which that’s literally physiologically possible.
ABDUS-SABOOR: That is very true. And what you’re talking at too is one of the reasons I got into pain and pain research. There’s a really nice book called The Challenge of Pain, written by Melzack and Wall, two really pioneering scientists in our field who came up with one of the most important theories in the history of pain: the “gate theory” of pain. But anyway, in this book, they lay out, like, as you’re getting to all these cases where people should be experiencing lots of pain, but they don’t. You know, some people who you can hypnotize them and their pain goes away.
And there are too many anecdotes like this to think that it’s not a real phenomenon. A related phenomenon that we do know a little bit more about, and people are starting to model this in rodents, which I think is really cool, is the placebo effect, which is very strong for pain actually.
If they have a strong expectation and belief that this thing will alter my pain, it can actually work. And conversely, if you tell someone, “I’m gonna give you this treatment and it hasn’t worked for anybody, everyone says it’s crappy, but you’re outta options, and I just wanna try it anyway.” They’ll come back and say, “Doc, you’re right. It didn’t work.” And it could be the same medicine, right?
So this expectation and belief of pain relief is very strong. We now know it definitely taps into our endogenous opioid system, our endogenous system to kind of control pain. It taps into these things. If you block like opioid receptor signaling, you can block many of these effects.
It’s not magic, but it’s acting on defined neuro circuits in the brain. And there are many labs that are hard at work, Greg Corder and Matt Banghart and Greg Scherrer, amongst others to try to map how this is working.
LEVIN: Amazing. I did see that you had talked about the pain addiction connection. Particularly with opioids.
ABDUS-SABOOR: Correct.
LEVIN: And what you’re saying is there’s a biological substrate reason why there’s a connection between pain and addiction.
ABDUS-SABOOR: Yes, that’s very true. We have an endogenous opioid system that can be activated by many things, and we have these opioid receptors all throughout our body.
I mean, the discovery of the opioid receptors back in the late 1970s, in rodents, they could stimulate this one area in the brain, the periaqueductal gray. And you could get really strong pain relief. The rat tail would be on the hot plate, and you stimulate this area in the brain. Then they don’t respond, okay? And they found that this area is, like, flooded with opioid receptors. And this response was, like, dependent upon activation of the endogenous opioid system.
Opioids can be powerful relievers of pain and the receptors are everywhere. This is why they also have so many unwanted side effects because they act on the pain system, but they act in the periphery, they act in the bladder, in the gut, in the DRG neurons, the spinal cord. They’re loaded everywhere, so they come with so many unwanted side effects beyond just pain relief.
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STROGATZ: Wow. So many surprising and very immediate things to think about there. I think anyone listening to this can relate.
LEVIN: Mm-hmm. I didn’t really appreciate that the opioids… Of course, I knew they were pain relievers, I guess. I knew that was the story. People were originally going to seek pain relief, but I thought it was a external consequence, you know? I didn’t think it was targeting the same biology.
That was really surprising to me, and that we have this endogenous, natural mechanism that can do the same thing, which is why it suggests we can overcome pain psychologically to some extent, you know? I guess it also just shines a light. There’s a lot we don’t understand about how our own minds work and bodies work.
STROGATZ: I believe it. Watch any magic trick, and you’ll see that. But no, I mean, in something as corporeal as pain, I mean, right? That’s not an illusion. And yet maybe some aspects of it are an illusion. It’s confusing.
LEVIN: Yeah, I don’t know that it’s an illusion. I mean, things are triggered. There are signals, right? But you can flood the receptors with other chemicals. I mean, that’s really what it sounded like to me. And it has an interesting evolutionary role, right, pain in terms of survival. It’s important that we don’t go running if our foot’s broken, and it is very disadvantageous to survival to have no pain receptors, and they know that there are certain people who don’t feel pain. So just appreciate when your back hurts at the sink, Steve.
STROGATZ: Yes, I see. I should be grateful for my pain receptors.
LEVIN: Exactly. Well, after the break, we’re gonna leave pain behind, and we’re gonna talk about something a little more pleasant, and that is the wonderful naked mole rat.
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LEVIN: Welcome back to The Joy of Why. We’re speaking with neuroscientist Ishmail Abdus-Saboor, who studies the brain and our sense of touch.
I do want to turn to your important work in antithesis to pain, which is about gentle touch and social touch and pleasing touch. So, I’m both curious what drew you in this other direction, and of course how the receptors involved in gentle touch or stroking touch are different from pain receptors and why this is so important in the social fabric of possibly both animals and humans.
ABDUS-SABOOR: Great question. You know, as I was ending my postdoctoral studies at UPenn and opening my lab about eight years ago, I started to think about, okay, who would want to come work in my research lab? And if I only have projects studying pain, maybe that could be off-putting. Could be some people who would prefer to study, you know, social touch, appetitive, something good. And that was the case, yeah.
I wanna pay homage to a colleague of mine, David Anderson, at Caltech. He published this paper that I read as a postdoc, and it was just so fascinating and exciting because what they had discovered was that there was a population of neurons that seemed to be activated by stroking touch on the mouse’s skin, consistent with these being pleasurable social touch detectors.
And that paper, they didn’t look in the brain, and they hadn’t linked it to like any behavior. So, I thought this was right for someone with my background and genetics and molecular manipulations, really careful analysis of behavior and also linking that with brain imaging. So, the thing that differs between these neurons and this pathway and pain is that it’s a different molecular population. These neurons happen to express, at least in a mouse, this gene called MRGPRB4. It’s a tongue twister. They do express Piezo channels, this other mechano sensor I told you that’s important. So, they’re definitely mechanosensory neurons.
What makes them special is their constellation of genes they express that’s different than some of the other classes that mediate other types of somatosensation. Their wiring where they’re, that they innervate the hairy skin areas that are, like, normally touched. The neurons that they’re connected to in the spinal cord and from spinal cord to the brain. Basically, the whole pathway from skin to brain is gonna be different than a pathway for like hot or cold or pain, okay. So, the whole, like, circuit, the anatomy, the wiring is totally different.
LEVIN: Wow. So highly specialized again.
ABDUS-SABOOR: Highly specialized again. For example, if you stimulate, like, a pain pathway to animals, like, quickly they give you signs that this is painful and they don’t like it, they avoid it. But with this pathway, they give us signs that they actually like it. They want to spend time in environments where this pathway is stimulated. And if we look at, for example, dopamine release in the brain’s reward center, we can see that stimulating this pathway in the skin leads to like this dopamine release or if we genetically ablated these neurons, we see social touch behaviors are greatly kind of diminished.
Now, some of our ongoing studies where we’re really excited, because this gets to your question again about, like, why it’s important and translational impact in humans. You know, we think this pathway is also important for the ability of touch to relieve stress and anxiety and depression.
When you’re down or going through some negative emotion, just think about a hug from a loved one, a parent, a friend. It can really calm you down, and make you feel better. We appreciate this phenomenon, but how it works at a molecular, cellular and neuronal level is almost completely unknown. The skin to brain pathway for social touch that we’ve been discovering and elucidating, we think could be important for that. And we have really strong evidence. It’s unpublished, but hopefully, you know, maybe later in this year we’ll submit this paper showing that activating this pathway can relieve negative states, which is really exciting. And we do think it has direct therapeutic potential. Maybe we can even think about treating diseases of the brain, chronic stress, not in the brain but by targeting neurons in the skin.
LEVIN: Wow. Fascinating. Now there’s this research that you’ve done where you have genetically altered mice to become sensitive to blue light so that instead of physically stroking them, you can illuminate them with this blue light, and they have the experience of being gently touched. So, I have many aspects to this question.
One is, what a crazy thing to do. That’s not a question. And the other is, you know, are we going to genetically alter human beings so that they can do blue light therapy as part of this, you know, attempt to heal certain disorders of the mind?
ABDUS-SABOOR: Yeah, it would be nice if we could get there one day. So, this technology is called optogenetics and I think it is one of the most important technologies in all of neuroscience. And hopefully there’s a Nobel prize on its way for some of our colleagues.
But anyway, this shows that the beauty of, like, evolutionary biology and looking across diverse species, there’s this protein and algae that allows the algae to propel through these muddy ponds to blue light. It’s an ion channel, a non-selective cation channel, which just basically means there’s a part of the protein that when blue light hits it, the channel opens, it allows positive ions to flood into the cell that expresses this protein.
This is, like, perfect for neurons. Neurons are electrically excitable cells that fire to positive ionic current flowing into the neuron. So, if you can put this special protein on the surface of your neuron through some sort of viral genetic engineering, you can confer the ability to directly activate these neurons in this way.
So, part of this project that we did some genetic engineering crossing mice together to put this blue light sensitive protein only in these neurons. And we can just shine light directly to the skin, as you mentioned to confer behavior.
Now, to do this in humans, one would have to get to a point where you could do, like, gene engineering to add this protein to cell types of interest.
People are doing this now to treat – this is not our work – but to treat like forms of retinal degeneration and blindness actually. It’s really incredible. So maybe there is a pathway for using this technology to treat people.
LEVIN: You were discussing similarities in how certain neural networks are working for mice and for human beings in some of these complex systems. But you famously work with naked mole rats and who doesn’t love a great naked mole rat colony? Please, for those who are not in the know of the extraordinary naked mole rat, can you describe them a little bit for us and, why their colonies are so unusual in the rodent kingdom.
ABDUS-SABOOR: Yeah, they’re amongst the most fascinating animals I’ve ever encountered. Some days we’re just like, “What are we studying?” Some days we literally just sit there and just stare at them.
LEVIN: Watch them?
ABDUS-SABOOR: Yes, yes, yes. Because their biology is so fascinating, but some of the things that really excite us about them.
So for one, they don’t feel many forms of pain, for reasons that are not fully clear. They seem to be immune or recalcitrant, unable to get cancer. They’re long lived for rodents, so they live about 30 to 40 years.
LEVIN: Wow, that’s a long lived rodent.
ABDUS-SABOOR: Yeah, yeah. Most mice and rats, they only live one to two years. Yeah. Yeah. And they don’t really have traditional signs of aging. So, when they die, they just die. You can’t look at ’em and age them. They don’t seem to have any like cognitive or physical decline. They just die.
And they’re highly social. And this is the thing that we really keyed in on my lab to date. In the last three plus years or so, we’ve been working with them. They’re actually the most social animals in the entire mammalian kingdom. So, one colony can contain dozens or hundreds of animals all living together and a really tight-knit colony. And they’re driven by this really single dominant queen, who’s the matriarch that kind of guides the whole society. And all the other animals are essentially workers and drones and are reproductively suppressed in the presence of the queen. She’s the only one who mates with one or two like breeding males in a colony. And she continues to give birth her entire life. So, no menopause or signs of slowing down. And so, as she has a litter, they never leave. The colony just gets bigger and bigger and bigger, okay. They’ve decided that it’s best for their survival of their colony to do everything together, okay.
They chiefly come from East Africa, Kenya, Ethiopia. They live completely underground as well. And the leading hypothesis is that, you know, maybe in this dry, arid desert climate, where food and resources are not plentiful, that it was easier to have a communal form of living such that some animals are foraging and hoping to stumble upon a tuber, like a sweet potato. And if they do, like the whole colony is alerted and they all can feed off that together.
LEVIN: It’s insect-like.
ABDUS-SABOOR: It’s very insect-like or bee-like, but they’re mammals, which is very interesting.
So, you know, we want to know like, how does this pain insensitivity work? How does you know this highly social life, like how is it set up? How is it maintained? How do they even recognize one another, especially because they’re essentially blind?
LEVIN: And they’re hairless, so there’s a lot of skin-to-skin contact.
ABDUS-SABOOR: There’s a lot of skin-to-skin contact. They crawl right over each other. They’re always touching. Even if you make the colony really big and you go to look at ’em, they’re always on top of each other. They just are always touching, you know?
And from our early studies and observations, it appears that, not saying other senses are not important, but touch is certainly outsized. You know, most of their sensory cortex seems to be dedicated to touch. So, they’ve lost the visual parts of their sensory cortex because they’re blind. But the somatosensory cortex, the touch cortex, has like encroached upon it.
So, we think they’re like touch specialists and they might be able to do things with touch that other seeing animals do with vision. Like communicate and recognize one another and know who it is that they’re interacting with.
LEVIN: Wow. Fascinating. And so, is there a sense in which we’re trying to understand human social interactions through touch by studying the naked mole rat? Or are these just two disparate fields of study?
ABDUS-SABOOR: I hope they’re not disparate fields of study. One could even make the case that their long-term stable relationships are more akin to human societies than a mouse, which is the predominant model system used to study these things, right?
We have long-term stable relationships. You know, people for 10 or 20 years, or you see a friend from college or whatever, you remember them. And these sorts of dynamic relationships that we see in their colonies we don’t see like in other animals. So, I think there are principles that we hope are very similar and could teach us about societies.
You know, I think one very exciting idea is that if we can learn like the principles, the genes, the molecules, the neural circuits, the neural networks that they use to like cooperate with one another and use shared resources like maybe some of that can be used to like inform human societies and how we can better cooperate given limited resources, for example.
LEVIN: In human societies, touch is a sensitive issue. Pardon the pun. But there’s an important role, obviously, that social touch plays, both aversion and appeal. Are you thinking about this in human society or is that kind of a meta level that you dream about maybe when you’re walking down the street, but isn’t really part of your actual research?
ABDUS-SABOOR: No, we do think about that. That question we’re actually trying to address on the mouse side of the lab, not in the naked mole rats. Maybe in the naked mole rats one day. But right now, we are working on this.
It’s really fascinating as you mentioned, right. If you’re in the comfort of your home and a loved one strokes you on the back or arm, it may feel good, but if you know you’re on the 1 train or something and someone touches you like that, right? You wanna recoil, and you know it’s not gonna feel good. But it could be the same touch to the skin. So then how does your brain know that this touch is in a good context and this is a bad context?
There must be some sort of gating in the brain that allows you to quickly approximate how you should respond. And how does that all work? It’s unclear, but I think we have good approaches to kind of study this.
Back to the mouse, I talked about those neurons we discovered as part of like that positive balance, social reward pathway. Now if we give animals mice that same stimulation, but we pair it, they’ve learned to associate with something negative like a shock. And now we do that optogenetic stimulation to activate the neurons. The animals don’t have a positive response; they have a negative response. So, we can easily dial in, like, good touch, bad touch in the animals and read this out.
So now we’re saying, “Well, how does this look in the brain?”, okay. There’s one area in the brain that we’ve become very excited about called the orbital frontal cortex, a frontal area, the front of the brain that appears to integrate sensory components and high level like learning and planning. And we think there might be neuro ensembles that are talking to other areas of the brain to let the animal know, like if the animal’s in a good state for a touch to be perceived as good, or if the animal’s somewhere where they’re afraid or anxious or have had a bad experience with it, such that now this gate to like the positive violence networks won’t be activated. So early days of this project, but we’re trying to figure out how this works at the level of the brain.
LEVIN: A lot of what you’re raising taps into, going back to metaphysics. So we began with Descartes, “I think therefore I am,” you know, consciousness is all important. Going down deep into genetics, molecular biology, neuroscience, and now it’s kind of to my mind, the questions start to come back again of how these neurons translate into this mental world, this interiority, this experience.
And I guess I just wonder how much at this scientific level you feel we can approach this really difficult question of why does it feel like something?
ABDUS-SABOOR: It is a wonderful question. And one of the things I’ll say is that I also have to appreciate my limitations as a molecular biologist, neuroscientist, right? Some of these questions may be slightly outside of the realm of where we can approach, you know, especially using a mouse model, right? I think there are mechanistic studies we can do in animals, but I do not think we can reach the highest levels of these high-level cognition and consciousness in a rodent model.
And this is where I think folks like me, we need to be interacting with cognitive scientists, people in psychology, people in other spaces. There’s too much of a disconnect between neuroscience and psychology. We’re not talking to one another, you know, but we’re both studying the brain and the mind, right. The neuroscientists tend to use animal models and are doing the work I talked about very mechanistic. Whereas the psychologists are doing really beautiful work, but they’re more tapped into, you know, the human experience.
The more we can talk to one another, I think we’ll be able to address these higher-level problems. And this is part of the institute I’m in, the Zuckerman Mind Brain Behavior Institute. Maybe this is a plug for our institute, but you know, this is something that we try to do because this is the only way we’re gonna solve the brain and the mind by bringing people together who think across skills.
LEVIN: Fascinating. I think you’ve portrayed this very well in your responses and in this conversation, which has just been so intriguing. But there’s a question we’d like to ask here at The Joy of Why, and that is what brings you the most joy or fulfillment in your work?
ABDUS-SABOOR: Yeah, I think I would answer that in two ways.
So one is just discovery, okay? When we have that kinda aha moment, that moment of insight where we say, “Oh my goodness, this is it.” For example, something we’re very excited about that we all can relate to is lactation, nursing that occurs in mammals, right? Now, we’ve known for a long time that, for example, with nursing, there’s a suckling stimulus on the skin from the child to the mom or the pup to the mom, and that physical suckling stimulus is enough to mediate milk release.
There’s like this neuroendocrine reflex that goes from the skin up to the brain back to the tissue. The milk comes down. The baby, the pup gets it. It all is initiated by, in part by touch, okay? But we had no idea, like what are the touch neurons that mediate that? In the last few months, we’ve been able to discover and put in a molecular handle. We found the neurons that mediate this. When we made this discovery, it was just like jumping for joy. It’s like the thing that we and others have been looking for for a very long time, like we cracked it, and the data looks so beautiful and convincing. Like, those are the moments that I really live for, where we can go from just not knowing to – at least at that moment – we might be the only people in the world who, like, have appreciated something.
Those are the moments that we live for. So, discovery is the thing that really drives me and brings joy to my life. And mentorship, right? Helping people achieve their dreams and goals in life and kinda working alongside them, I also live for that, too, and sometimes that’s just as like exciting for me as discovery.
LEVIN: Thank you so much for taking the time to bring those ideas out of the lab and share them with us and with our audience. It’s just been a pleasure, Ishmail. Thank you.
ABDUS-SABOOR: Thank you. You’ve been great. you’ve really pulled a lot out of me today. Thank you.
STROGATZ: I’m smiling at that, and so are you, Janna. We can see each other here, and I just, I had a feeling that he would say something about, “At that moment, I’m the only person,” or, “My team is the only team in the world.” There is something about that. It’s not exactly vanity, but I think every scientist feels that, every mathematician, right?
I mean, is that why you were smiling when he said that?
LEVIN: Oh, yeah. Well, also he was such a lovely person, you know? And you just, you enjoyed that he enjoyed it. You know that he had this wonderful moment of discovery and I also thought it was incredibly fascinating how he was talking about the speciation of the actual neurons. Like, they’re specialized, and they’re not these generic neurons, but they’re intended for these purposes. I mean, I just thought that was also really fascinating, and you can imagine that moment of discovery was just tremendous for them.
Anyway, wonderful stuff. I’ll give you a hug next time I see you.
STROGATZ: Very good. I might recoil. Touch is a big thing for me. So don’t take it personally.
LEVIN: Oh my God. That’s hilarious. I’m gonna come at you with such a bear hug next time.
STROGATZ: Come at me!
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STROGATZ: If you’re enjoying The Joy of Why and you’re not already subscribed, hit the subscribe or follow button wherever you’re listening. You can also leave a review for the show. It helps people find this podcast. Find articles, newsletters, videos and more at QuantaMagazine.org.
LEVIN: The Joy of Why is a podcast from Quanta Magazine, an editorially independent publication supported by the Simons Foundation. Funding decisions by the Simons Foundation have no influence on the selection of topics, guests or other editorial decisions in this podcast or in Quanta Magazine.
The Joy of Why is produced by PRX Productions. The production team is Caitlin Faulds, Jade Abdul-Malik, Genevieve Sponsler, and Merritt Jacob. The Executive Producer of PRX Productions is Jocelyn Gonzales. Edwin Ochoa is our project manager.
From Quanta Magazine, Simon Frantz and Samir Patel provided editorial guidance, with support from Samuel Velasco, Simone Barr, and Michael Kanyongolo. Samir Patel is Quanta’s Editor-in-Chief.
The episode art is by Chanelle Nibbelink and our logo is by Jaki King and Kristina Armitage. Special thanks to Garth Avery at the Cornell Broadcast Studio.
I’m your host, Janna Levin. If you have any questions or comments, please email us at [email protected]. Thanks for listening!
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