How Does Touch Lead To Pain Or Pleasure?

Pain and pleasure seem like simple facts of life, however they are anything but that.

痛苦和快乐似乎是生活中简单的事实，但事实并非如此。

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.

例如，神经科学家仍然无法解释为什么身体疼痛与心理疼痛不同，或者为什么亲人的触摸会带来舒缓，而陌生人的触摸会令人厌恶。

To explore the science behind these sensations, Janna Levin talked to Ishmail Abdus-Saboor , a neuroscientist at Columbia University’s Zuckerman Institute.

为了探索这些感觉背后的科学原理，Janna Levin 与哥伦比亚大学祖克曼研究所的神经科学家 Ishmail Abdus-Saboor 进行了交谈。

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.

他们的谈话涵盖了疼痛如何服务于进化目的，研究人员如何在没有任何客观生物标记的情况下在实验室中测量疼痛和快乐，以及触摸如何作为一种社会和情感信号而不仅仅是一种感觉信号。

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.

阿卜杜斯-萨布尔还描述了他对裸鼹鼠的研究——裸鼹鼠几乎感觉不到疼痛，没有衰老迹象，生活在几乎完全依靠触摸的群体中——以及在研究无法描述自己感受的动物的感觉时的伦理权衡。

Listen on Apple Podcasts , Spotify , TuneIn or your favorite podcasting app, or you can stream it from Quanta .

在 Apple 播客、Spotify、TuneIn 或您最喜爱的播客应用程序上收听，或者您也可以从 Quanta 进行流式传输。

I was very fascinated about biology and biological systems and how animals communicate and cooperated.

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。

The language in which they’re operating is data, observations.

他们操作的语言是数据和观察。

You know, it’s more immediate to their experiments.

你知道，这对他们的实验来说更直接。

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.

但我不得不说，当你提到快乐和痛苦时，我有一点恶心的感觉，尤其是作为一个家里有动物的人。

My dog, Murray, that I love so much.

我的狗穆雷，我非常爱它。

But even then, I think animal experimentation, even in the most benign sense, is called into question.

但即便如此，我认为动物实验，即使是在最善意的意义上，也受到了质疑。

And he thinks about the ethics of that.

他思考了这样做的道德问题。

Well, let me introduce our guest.

好吧，让我介绍一下我们的客人。

His name is Ishmail Abdus-Saboor.

他的名字叫伊什梅尔·阿卜杜斯·萨布尔。

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.

他是哥伦比亚大学祖克曼研究所的一名神经科学家，他研究皮肤-大脑轴，特别是我们的触觉，包括轻柔的触摸和舒缓的触摸。

I had many pets growing up, dogs and cats, but also like lizards and turtles and snakes.

我从小养过很多宠物，有狗和猫，也有蜥蜴、乌龟和蛇。

You know, I remember, like, as a kid having this subscription to this, like, Turtle Digest sort of a magazine.

你知道，我记得，小时候订阅过《海龟文摘》之类的杂志。

You know, I was very fascinated about biology and biological systems and how animals communicate and cooperate.

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。

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.

我认为我的科学生涯是在高中一年级时认真开始的，正如你提到的，在费城中央高中，作为荣誉生物课的一部分。

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.

你知道，实际上，我们没有上体育课，因为要报名学习荣誉生物课，我们必须上两节生物课。

And for me, even as a 14-year-old kid, like, I just jumped at that opportunity.

对我来说，即使作为一个 14 岁的孩子，我也只是抓住了这个机会。

You know, who needs gym?

你知道，谁需要健身房？

Got teased a little bit.

有点被嘲笑了。

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.

但是，你知道，作为该项目的一部分，我们能够进行为期一年的科学博览会项目，许多学生在费城、坦普尔、德雷克塞尔或宾夕法尼亚大学的邻近大学工作。

But we also were able to do science at home.

但我们也能够在家做科学。

So this is what I did.

这就是我所做的。

You know, basic rudimentary equipment and things.

你知道，基本的基本设备和东西。

And the project was actually looking at regeneration in crayfish.

该项目实际上是在研究小龙虾的再生。

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.

所以你知道，我的父母非常支持我，让我接管我们位于费城日耳曼敦区的房子的三楼。

And, you know, there were hundreds of crayfish and I’m sure it didn’t smell so well up there.

而且，你知道，那里有数百只小龙虾，我确信那里的味道不太好。

But at the time, you know, there was this really big push on, like, supplements and ginseng.

但当时，你知道，补充剂和人参等产品受到了很大的推动。

And like ginseng was supposed to be like this magical supplement that, like, improved health and memory and all sorts of wonderful things.

就像人参应该是这种神奇的补品一样，可以改善健康和记忆力以及各种奇妙的东西。

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.

所以我的想法是，如果我在小龙虾及其水中加入这种人参草药补充剂，那么这可以加快再生速度，因为它们确实有能力再生失去的附属物。

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.

所以，你知道，我必须成为一名科学家，我喜欢修剪它们的附肢的一部分并测量它的生长速度。

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.

而且，这是一个非常令人兴奋的时刻，我保留了一个实验室笔记本，并提出了我可以测试的假设，制作了图表，绘制了我的数据，并进行了统计测试，看看这里是否有什么东西。

Unfortunately, I don’t quite remember the outcome of those.

不幸的是，我不太记得这些的结果。

But you ended up studying smaller-scale biology, cellular, molecular.

但你最终研究了较小规模的生物学、细胞、分子。

What led you to make that transition from this sort of love of animals to the actual smaller-level biology?

是什么促使你从对动物的这种热爱转向真正的较小层面的生物学？

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.

所以我在很多兽医诊所和医院工作过，在那里我的经历就是帮助兽医进行绝育手术，这非常单调，而且坦率地说，非常无聊。

And I kinda missed, like, this kinda fast-paced nature of biological exploration.

我有点怀念生物探索的快节奏本质。

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.

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进行了另一次实习，我们在那里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。

Many times we downplay animal intelligence or cognition because we don’t know how to tap into it.

很多时候，我们低估动物的智力或认知，因为我们不知道如何利用它。

We haven’t designed the right test.

我们还没有设计出正确的测试。

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.

在那里，我接触到了分子生物学研究和工作台工作，以及科学文化，整个科学学科的精神，在实验室会议上和人们展示结果，以及谈论所有悬而未决的问题，并且能够从分子、DNA、RNA，你知道，生命分子的尺度来观察生命。

I thought that was just very exciting.

我认为这非常令人兴奋。

It wasn’t until a few years later that I moved into, like, neuroscience and sensory neuroscience.

直到几年后，我才进入神经科学和感觉神经科学等领域。

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.

你对我们如何从这种身体上的疏离过渡有何理解，正如我们在广达的同事所说，“他们不思考，因此他们不存在。”这就是他接受动物感受到疼痛的态度。

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?

那么，如果我们将其归结为疼痛的概念及其作用原理以及动物是否感到疼痛的界限在哪里？

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.

这是一场持续多年的争论，我认为现代的想法是，你需要一个大脑，你需要一些中央处理单元来拥有完整的功能和认知，才能体验疼痛。

If you look at lower animals, perhaps, no one denies that they can sense nociception.

如果你观察一下低等动物，也许没有人会否认它们能够感受到伤害。

Nociception, it’s a fancy term for receptors, neurons, out in the peripheral nervous system that can be activated by noxious stimuli.

伤害感受，这是一个奇特的术语，指的是周围神经系统中的受体、神经元，可以被有害刺激激活。

And those signals travel to some central processing units so that the animal knows to like move away.

这些信号传输到一些中央处理单元，以便动物知道喜欢走开。

And I think this idea, everyone appreciates.

我认为这个想法得到了每个人的赞赏。

Even simple, you know, bacteria, right, single cell organisms if you put them in an environment that’s not conducive, they’ll move away.

即使是简单的，你知道的，细菌，对，单细胞生物，如果你把它们放在一个不有利的环境中，它们就会离开。

They’ll recoil, because they have sensory neurons out in their peripheral nervous system.

他们会后退，因为他们的周围神经系统中有感觉神经元。

Now, we would consider that nociception, but not quite pain.

现在，我们会考虑伤害感受，但不完全是疼痛。

Encapsulate the experience of pain, you have to have a central processing unit whereby you can respond appropriately to subsequent noxious stimuli.

概括疼痛的经历，你必须有一个中央处理单元，以便你可以对随后的有害刺激做出适当的反应。

There’s some sort of learning and memory.

有某种学习和记忆。

There’s higher level cognition.

还有更高层次的认知。

You understand that this particular stimulus that I’ve received, like, causes me pain, so now I’m going to avoid it.

你知道我收到的这种特殊刺激会给我带来痛苦，所以现在我要避免它。

So then the debate is, if that’s the case, then which animals have it and which animals do not?

那么争论的焦点是，如果是这样的话，那么哪些动物有，哪些动物没有？

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.

我认为，作为一个神经科学界，总的来说，我们的想法是，许多动物，尤其是低等动物，可能不具备那种更高水平的认知和意识。

You know, a question I get all the time, right, people, especially in the New England area, they ask about lobsters, right?

你知道，我一直被问到这个问题，对吧，人们，特别是在新英格兰地区，他们会问有关龙虾的问题，对吗？

Should I feel bad about throwing this lobster in this hot boiling pot while it’s still alive?

当龙虾还活着的时候，把它扔进滚烫的锅里，我应该感到难过吗？

So as a field, like the classical test that we do is like this conditioned place aversion.

因此，作为一个领域，就像我们所做的经典测试一样，就像这种条件性地方厌恶。

So does an animal have enough brain real estate to understand that this thing is noxious?

那么动物是否有足够的大脑空间来理解这个东西是有毒的呢？

They should be able to understand that the environment that they received this noxious stimulus is bad.

他们应该能够明白，他们受到这种有害刺激的环境是不好的。

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.

这样，如果你以后把他们放在那个环境中，他们就会记住我在这里收到的东西不好，我想逃避或避免它。

Animals that don’t have that cognitive ability, even though they’ll recoil from something noxious.

没有这种认知能力的动物，尽管它们会对有毒的东西感到畏惧。

They don’t have the ability to form the memory, a conscious perception, the negative feeling that is attributed to pain, right?

他们没有能力形成记忆、有意识的感知、归因于疼痛的负面感觉，对吗？

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?

这就是人们所做的，如果你可以进行这个测试并表明他们可以建立这些关联，那么人们就会说：“你知道吗？

I think this animal can feel pain, and let’s add that animal to the list.”

我认为这种动物能够感受到疼痛，让我们将这种动物添加到列表中。”

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.

这是我认为我的一些工作的重要性的一部分，因为我们对动物在经历不同刺激时的行为进行了非常详细的绘制。

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.

我们可以说，实际上他们的反应方式无法向我们描述他们持续的情绪状态，但如果我们可以用行为来解读他们的内部状态，他们就会表现出非常典型的痛苦消极情绪状态的行为，而我们正试图在大脑中绘制出这种地图。

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.

你让我想起了我的一位同事、加州大学圣地亚哥分校和索尔克研究所的 Kay Tye 教授的一些工作。

In rodents, she’s asking this question, physical pain and emotional, psychological pain do they map or intersect anywhere in the brain?

在啮齿类动物中，她问了这个问题，身体疼痛和情感、心理疼痛它们是否映射或交叉在大脑的任何地方？

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.

她设计了一个非常聪明的测试，她将其称为老鼠的 FOMO 任务，即害怕错过的感觉，她会让老鼠住在一起。

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.

她在它们之间放了一个隔板，隔板外面的动物必须坐在那里，看着它的朋友们得到，比如，巧克力奶昔。

Okay, so the mouse is just watching its friends.

好吧，所以老鼠只是在观察它的朋友。

The mouse is a little bit hungry, a little bit thirsty, and watching his friends take this milkshake.

老鼠有点饿，有点渴，看着他的朋友们喝这杯奶昔。

And her idea is that this is like a psychological form of pain.

她的想法是，这就像一种心理形式的疼痛。

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?

然后她在大脑中称为岛叶皮层的部分进行录音，并提出这样的问题：这会与身体疼痛相互作用吗？

And it appears that it does.

看来确实如此。

Like it alters their threshold to respond to, like, physical pain after going through this emotional psychological pain.

就像它改变了他们在经历这种情感心理痛苦后对身体疼痛做出反应的阈值一样。

And maybe that there’s similar constructs in the brain, and we can even study this in a rodent.

也许大脑中也有类似的结构，我们甚至可以在啮齿动物身上研究这一点。

We had a basic idea of the neuroanatomical pathways.

我们对神经解剖学通路有了基本的了解。

So, you have these peripheral sensory neurons called, uh, they emanate from a structure called the dorsal root ganglia.

所以，这些外周感觉神经元被称为，呃，它们源自一种称为背根神经节的结构。

And we have, like, 30 pairs of these that run alongside our spinal cord.

我们有大约 30 对这样的神经元，它们沿着我们的脊髓延伸。

They send one long process to the skin or other internal organs and one process to the spinal cord.

它们将一个长进程发送到皮肤或其他内脏器官，并将一个进程发送到脊髓。

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.

从脊髓，一组不同的神经元接收中继信号，到达脑干，然后从大脑底部到达整个大脑的其他区域。

So, the neuroanatomical pathways, we kind of have had this for quite some time.

所以，神经解剖学通路，我们已经有相当长一段时间了。

But as you mentioned, there’s touch, there’s hot, there’s cold, there’s itch, like these are quite distinct.

但正如你提到的，有触摸，有热，有冷，有痒，就像这些是非常不同的。

So, it’s where the specificity resides that allows us to exquisitely detect these different sensations.

因此，正是这种特殊性让我们能够精确地察觉到这些不同的感觉。

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.

你知道，我们的领域在过去 15、20 年里发生了一场非常好的革命，在周围神经系统的这些感觉神经元中，我们已经识别出了赋予特异性的受体蛋白。

And two of the most famous ones I’ll just mention because they were the subject of a Nobel prize in 2021.

我只提其中最著名的两个，因为它们是 2021 年诺贝尔奖的主题。

So, one was the discovery of a receptor protein called, um, TRPV1.

因此，其中之一就是发现了一种名为 TRPV1 的受体蛋白。

Transient Receptor Potential Vanilloid 1.

瞬时受体电位香草酸 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?

这是大卫·朱利叶斯（David Julius）的实验室发现的，他着手确定辣椒，比如为什么我们认为它们很辣？

We had an idea of which neurons may do it, but like, how do you explain the “how” at a molecular level?

我们知道哪些神经元可以做到这一点，但是，你如何在分子水平上解释“如何”？

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.

因此，他设计了一个非常巧妙的筛选，将受体克隆到细胞系中，并基本上应用了辣椒素（辣椒中的活性成分）。

And he wanted to find cells whereby once you add capsaicin, there can be like an intracellular response.

他想找到细胞，一旦添加辣椒素，就会产生类似细胞内的反应。

They can be activated in the form of calcium entry into the cell, which is a proxy for, like, neuroactivity.

它们可以以钙进入细胞的形式被激活，细胞是神经活动的代表。

As a field, I think we’ve made, and are making, really great progress.

作为一个领域，我认为我们已经取得了并且正在取得巨大的进步。

And this activity can be conferred by adding a certain receptor protein.

而这种活性可以通过添加某种受体蛋白来赋予。

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.

因此，他筛选并基本上找到了我们现在称为 TRPV1 的通道，当它在细胞表面表达时，赋予其对辣椒素做出反应的能力。

We now know, and they showed in that paper, that this same receptor mediates the response to heat.

我们现在知道，并且他们在那篇论文中表明，同样的受体介导对热的反应。

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.

所以，这就是为什么辣椒素和辣椒有这种热感，因为也对辣椒素做出反应的热感神经元表达了这种蛋白质。

This paper came out like in 1999, I believe.

我相信这篇论文是在 1999 年发表的。

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.

它真正开始了疼痛研究的分子时代，因为现在我们有了一种受体，我们可以说，好吧，如果它表达这种 TRPV1 受体，这就是你定义疼痛神经元或热感神经元的方式。

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.

现在，那是 20 世纪 90 年代末，几年后，Ardem Patapoutian 实验室（与 David Julius 共同获得 2021 年诺贝尔奖）又进行了一项开创性研究。

He did a similar sort of a screen in a different cell line looking for receptor proteins that confer mechanical sensation.

他在不同的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。

Okay.

好的。

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.

他们做了一个稍微不同的筛选，他们使用 RNAi 来敲低细胞系中受体蛋白的表达，他们知道这些受体蛋白对机械力敏感，并且可以表明，如果没有这一种或两种蛋白，细胞将不再对机械力做出反应。

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.

我们现在将这些基因称为 Piezo1 和 Piezo2，在大多数情况下，我们所知道的几乎每个神经元都是机械敏感的，这意味着可以将物理刺激能量转换为神经系统的语言，即电活动。

It’s conferred by this mechanical sensor Piezo.

这是由压电机械传感器赋予的。

And it’s not just in neurons; it’s in non-neuronal cells.

这不仅存在于神经元中，也存在于神经元中。它存在于非神经元细胞中。

So here’s another example.

这是另一个例子。

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.

我刚刚给你举了两个例子，它们是感觉神经元，但如果这个神经元有 TRPV1，它就会对热、有害的热做出反应。

And if this one has Piezo, it’s gonna respond to pressure.

如果这个有压电，它就会对压力做出反应。

And there are other sorts of receptors that confer itch or cold, et cetera.

还有其他类型的受体可以带来瘙痒或寒冷等。

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.

现在作为一个领域，如果我跳到 2026 年，我们的领域刚刚再次将大脑奖授予了哈佛大学的 David Ginty 和欧洲的 Patrik Ernfors 教授，这是神经科学领域的最大奖项。

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.

他们做了真正开创性的工作，证明这些疼痛、触觉、瘙痒神经元至少有 15 种不同类别，这些神经元是根据不同基因的表达、生理特性和皮肤内的表达模式来定义的。

As a field, I think we’ve made, and are making, really great progress.

作为一个领域，我认为我们已经取得了并且正在取得巨大的进步。

So you know, what’s left to do, and why am I still employed?

所以你知道，我还剩下什么要做，为什么我仍然受雇？

You know, I think, as a field, we’ve learned a lot about detection in the periphery.

我认为，作为一个领域，我们已经了解了很多有关外围检测的知识。

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?

在实验室工作中真正推动我前进的事情之一是在周围神经系统、皮肤中的所有这些机制之间建立联系，以及它如何与感知所在的大脑联系起来，对吗？

Making the connection.

建立连接。

This body, brain, physiology, and signaling.

这个身体、大脑、生理学和信号传导。

This is where I think the next wave of major discoveries we’re ripe for in this field.

我认为这就是我们在这个领域的下一波重大发现已经成熟的地方。

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.

在我们的一些研究之前，我们在该领域的情况就像是，你用你认为痛苦的东西戳动物，如果它们做出反应，它们就会感到痛苦。

If they don’t, they’re not in pain.

如果他们不这样做，他们就不会感到痛苦。

Pain is so complex, right?

疼痛是如此复杂，对吗？

Just think if someone, like, poked you and looked at whether you lifted your hand, would that be sufficient to explain your pain state?

试想一下，如果有人戳你一下，看看你是否举起了手，这足以解释你的疼痛状态吗？

No. It’s so much richer.

不，它丰富得多。

So, this is what we attempted to do with this rodent pain scale to put a number on their sensation.

因此，这就是我们尝试用啮齿动物疼痛量表来对它们的感觉进行量化的方法。

We don’t have that.

我们没有那个。

We’re searching.

我们正在寻找。

We and everyone in the field is searching, but we don’t have it.

我们和该领域的每个人都在寻找，但我们没有。

In the clinic, we have to rely on self-reports.

在临床上，我们必须依靠自我报告。

People largely telling us how they feel.

人们主要告诉我们他们的感受。

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.

在功能磁共振成像和其他大脑成像方法等方面已经取得了一些进展，看起来很有希望，也许我们有一天会出现一个标志，我们可以自信地说某人正处于痛苦之中，而不是处于其他状态。

But we don’t have that yet.

但我们还没有。

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?

这对于研究疼痛的人来说是一个挑战，因为我们必须诱发疼痛才能研究它，对吗？

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.

我认为我们的行为分析的好处之一是，因为我们现在获得了如此多的分辨率，所以我们可以测试更少的动物来得出我们的统计观察和结论。

So, this kind of helps with animal welfare.

所以，这有助于动物福利。

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.

我们尽最大努力人道和尊重地对待动物，因为我们确实理解它们经常为了人类的利益而献出生命。

And this is just something that we have to appreciate.

这正是我们必须欣赏的。

We need medicines, we need cures, we need treatments.

我们需要药物，我们需要治疗，我们需要治疗。

And oftentimes animal research is a part of that pipeline.

通常，动物研究是该管道的一部分。

And I’m comfortable ethically with that understanding.

我在道德上对这种理解感到满意。

Now I know there’s some people who are not.

现在我知道有些人不是。

And it’s not upon me to convince people to change their beliefs or thoughts.

我不应该说服人们改变他们的信仰或想法。

I respect those.

我尊重那些。

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.

有人说：“我喜欢你所做的研究，但从道德上讲，这不适合我。”我也理解这些担忧。

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.

但我认为，到 2026 年，我们仍然需要动物了解疼痛系统的工作原理以及如何设计缓解慢性疼痛的安全方法。

And we don’t have better models to do this, so we have to work responsibly and ethically in these animal models.

我们没有更好的模型来做到这一点，所以我们必须在这些动物模型中负责任地、合乎道德地工作。

Now, will that change?

现在，这种情况会改变吗？

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?

是否有一天，我们可以使用计算机模型、刺激或类器官模型，并像在动物模型中一样学到更多东西？

Maybe that day will come and we’ll have to revisit this.

也许那一天会到来，我们将不得不重新审视这一点。

Maybe there won’t be a day where we can continue to justify using animals to study pain or in neuroscience research.

也许有一天我们不会继续证明使用动物来研究疼痛或神经科学研究是合理的。

But I don’t think that day has arrived and they’re still very important conduits to study.

但我认为这一天还没有到来，它们仍然是非常重要的学习渠道。

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.

我确实相信，我们对公众和资助我们研究的纳税人有责任思考我们正在做的基础工作如何转化为疗法和治愈方法。

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?

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，特别是针对疼痛，对吗？

There are millions of people who suffer with chronic pain.

有数百万人患有慢性疼痛。

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?

在啮齿动物身上进行研究的美妙之处在于，我谈到的许多基因和分子以及神经元通路都是高度保守的，对吧？

The wiring and the neuroanatomy of the pain system is very much shared between rodents and humans, okay?

疼痛系统的接线和神经解剖结构在啮齿类动物和人类之间非常相似，好吗？

We really do operate under the space that some of the things we discover can have direct application.

我们确实在我们发现的一些东西可以直接应用的空间下进行操作。

I’ll just mention an exciting example.

我只提一个令人兴奋的例子。

Some papers in the early 2000s in humans showed that there was a family of patients who can’t feel any pain whatsoever.

2000 年代初期的一些针对人类的论文表明，有一个患者家庭完全感觉不到任何疼痛。

And there have been these rare cases throughout history of people who just don’t feel any pain.

历史上有过一些罕见的案例，人们感觉不到任何疼痛。

It’s actually, like, not a good thing because many of these patients don’t live long lives.

实际上，这并不是一件好事，因为许多患者的寿命并不长。

They actually injure themselves.

他们实际上伤害了自己。

You know, pain is, from an evolutionary perspective, good for our bodies.

你知道，从进化的角度来看，疼痛对我们的身体有好处。

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.

不管怎样，巴基斯坦有一个家庭没有感到任何疼痛，所以你可以进行基因研究并追踪疼痛和敏感性。

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.

科学家们去了那里，做了非常英勇的工作，他们对他们的 DNA 进行了测序，发现他们的一个基因都有突变。

It’s called Nav1.7.

它被称为 Nav1.7。

It’s a voltage-gated sodium channel, okay?

这是电压门控钠通道，好吗？

This channel, this protein, seems to be very specific to pain neurons in the periphery.

这种通道、这种蛋白质似乎对周围的疼痛神经元非常特异。

So if people don’t have a functional version of this protein, they won’t feel pain.

因此，如果人们没有这种蛋白质的功能版本，他们就不会感到疼痛。

And then conversely, there’s another class of patients that have the exact opposite.

相反，还有另一类患者的情况恰恰相反。

It’s called, like, Burning Man syndrome, where they just have spontaneous pain, mainly in their extremities throughout life.

这被称为“火人节综合症”，他们一生中都会出现自发性疼痛，主要是四肢疼痛。

It turns out the mutation is in the same protein.

事实证明，突变是在同一个蛋白质中。

This one protein, you don’t have it, no pain.

这种蛋白质，你没有它，就没有痛苦。

Too much of it, lots of pain.

太多了，很多痛苦。

Same thing happens in rodents and many other mammals we’ve studied.

同样的情况也发生在啮齿动物和我们研究过的许多其他哺乳动物身上。

This voltage gated sodium channel is very important for the activity of the neuron propagating an action potential and specifically in pain neurons.

这种电压门控钠通道对于传播动作电位的神经元的活动非常重要，特别是在疼痛神经元中。

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.

事实上，它们是经过改进的新药，实际上可以阻断这种特定的受体，并且似乎可以改善许多患者的疼痛。

There’s another version of this protein called Nav1.8 that seems to have similar functions.

这种蛋白质的另一个版本称为 Nav1.8，似乎具有类似的功能。

So maybe some of the therapies in the future, we’ll kind of do a double block of both of these proteins.

所以也许在未来的一些疗法中，我们会对这两种蛋白质进行双重阻断。

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.

这项工作，其中很多是在啮齿类动物身上进行的，这是一个例子，展示了动物研究和实际直接翻译之间的来回和串扰。

One of the things we’re very excited about doing in my lab, I mentioned these behavioral tools.

我提到了这些行为工具，这是我们在实验室做的非常兴奋的事情之一。

And with our behavioral tools we can delineate in rodents the sensory component of pain versus more emotional components of pain.

通过我们的行为工具，我们可以在啮齿类动物中描绘疼痛的感觉成分和疼痛的情感成分。

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.

因此，大脑中似乎确实存在一个情感网络——杏仁核、前扣带皮层、岛叶皮层和其他一些似乎赋予疼痛情感成分的区域。

How that works, you know, we and others are hard at work.

你知道，这是如何运作的，我们和其他人正在努力工作。

But the point I wanna make, back to your question about translation.

但我想说的一点是，回到你关于翻译的问题。

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.

如果我们未来的疗法不针对周围神经系统水平、感觉水平的疼痛，而是在知觉水平上改变疼痛，甚至可能改变疼痛的负面情绪状态，那就太好了。

Because maybe you don’t want a world where you can’t feel any pain, as we mentioned, it does serve some purpose, right?

因为也许你不想要一个感觉不到任何痛苦的世界，正如我们提到的，它确实有某种目的，对吧？

But, if we can remove the hurting component but keep the sensory intact, then maybe this is how we want to tackle pain.

但是，如果我们能够消除伤害成分，但保持感觉完整，那么也许这就是我们想要解决疼痛的方式。

But we have to know how that works at a deep level to be able to kind of target that.

但我们必须知道它是如何在深层次上发挥作用的，以便能够瞄准这一目标。

But I can envision a future where that’s possible.

但我可以想象一个有可能实现的未来。

And there are too many anecdotes like this to think that it’s not a real phenomenon.

而且这样的轶事太多了，以至于不能认为这不是一个真实的现象。

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.

我们确实了解更多的一个相关现象，人们开始在啮齿类动物中建立这种模型，我认为这真的很酷，那就是安慰剂效应，它实际上对疼痛非常强烈。

If they have a strong expectation and belief that this thing will alter my pain, it can actually work.

如果他们强烈期望并相信这件事会改变我的痛苦，那么它确实可以发挥作用。

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.

相反，如果你告诉某人，“我要给你这种治疗方法，但它对任何人都不起作用，每个人都说它很糟糕，但你别无选择，无论如何我只想尝试一下。”他们会回来说：“医生，你是对的。

It didn’t work.” And it could be the same medicine, right?

没用。”而且可能是同一种药，对吗？

So this expectation and belief of pain relief is very strong.

所以这种缓解疼痛的期待和信念是非常强烈的。

We now know it definitely taps into our endogenous opioid system, our endogenous system to kind of control pain.

我们现在知道它肯定会利用我们的内源性阿片系统，我们的内源性系统来控制疼痛。

It taps into these things.

它利用了这些东西。

If you block like opioid receptor signaling, you can block many of these effects.

如果你阻断阿片受体信号传导，就可以阻断其中许多效应。

It’s not magic, but it’s acting on defined neuro circuits in the brain.

这不是魔法，但它作用于大脑中特定的神经回路。

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.

许多实验室都在努力工作，例如 Greg Corder、Matt Banghart 和 Greg Scherrer 等，试图绘制出其工作原理。

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, but alter it at the level of perception.

如果我们未来的疗法不针对周围神经系统水平的疼痛，而是在感知水平上改变疼痛，那就太好了。

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.

我的意思是，早在 20 世纪 70 年代末就在啮齿动物中发现了阿片类受体，它们可以刺激大脑中的这一区域，即导水管周围灰质。

And you could get really strong pain relief.

而且你可以获得真正强烈的疼痛缓解。

The rat tail would be on the hot plate, and you stimulate this area in the brain.

老鼠尾巴放在热板上，你刺激大脑的这个区域。

Then they don’t respond, okay?

然后他们就不回复了，好吗？

And they found that this area is, like, flooded with opioid receptors.

他们发现这个区域充满了阿片受体。

And this response was, like, dependent upon activation of the endogenous opioid system.

这种反应依赖于内源性阿片类药物系统的激活。

Opioids can be powerful relievers of pain and the receptors are everywhere.

阿片类药物可以有效缓解疼痛，而且受体无处不在。

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.

这就是为什么它们也有这么多不需要的副作用，因为它们作用于疼痛系统，但它们作用于外周，它们作用于膀胱、肠道、DRG 神经元、脊髓。

They’re loaded everywhere, so they come with so many unwanted side effects beyond just pain relief.

它们到处都有，所以除了缓解疼痛之外，它们还带来了许多不需要的副作用。

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?

这真的让我感到惊讶，我们有这种内源性的自然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克服心理上的痛苦，你知道吗？

I guess it also just shines a light.

我想它也只是发出光芒。

There’s a lot we don’t understand about how our own minds work and bodies work.

关于我们自己的思想和身体如何运作，我们还有很多不了解的地方。

I do want to turn to your important work in antithesis to pain, which is about gentle touch and social touch and pleasing touch.

我确实想谈谈你与痛苦​​相对立的重要工作，这是关于温柔的接触、社交接触和令人愉悦的接触。

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.

所以，我很好奇是什么吸引你朝另一个方向发展，当然，参与温柔触摸或抚摸触摸的感受器与疼痛感受器有何不同，以及为什么这在动物和人类的社会结构中如此重要。

I wanna pay homage to a colleague of mine, David Anderson, at Caltech.

我想向我在加州理工学院的同事大卫·安德森（David Anderson）致敬。

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.

他发表了我作为博士后读过的这篇论文，它是如此令人着迷和令人兴奋，因为他们发现，有一群神经元似乎通过抚摸老鼠皮肤而被激活，这与这些令人愉悦的社交触摸探测器一致。

And that paper, they didn’t look in the brain, and they hadn’t linked it to like any behavior.

在那篇论文中，他们没有观察大脑，也没有将其与任何行为联系起来。

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.

所以，我认为这对于具有我的背景、遗传学和分子操作的人来说是正确的，对行为进行了非常仔细的分析，并将其与大脑成像联系起来。

So, the thing that differs between these neurons and this pathway and pain is that it’s a different molecular population.

因此，这些神经元、这条通路和疼痛之间的不同之处在于它是不同的分子群。

These neurons happen to express, at least in a mouse, this gene called MRGPRB4.

这些神经元恰好表达（至少在小鼠体内）这种名为 MRGPRB4 的基因。

It’s a tongue twister.

这是一个绕口令。

They do express Piezo channels, this other mechano sensor I told you that’s important.

它们确实表达了压电通道，这是我告诉过你的另一个机械传感器，这很重要。

So, they’re definitely mechanosensory neurons.

所以，它们肯定是机械感觉神经元。

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.

它们的独特之处在于它们表达的基因群与介导其他类型躯体感觉的其他一些类别不同。

Their wiring where they’re, that they innervate the hairy skin areas that are, like, normally touched.

它们的布线就在它们所在的地方，它们支配着通常被触摸的毛茸茸的皮肤区域。

The neurons that they’re connected to in the spinal cord and from spinal cord to the brain.

它们连接到脊髓中以及从脊髓到大脑的神经元。

Basically, the whole pathway from skin to brain is gonna be different than a pathway for like hot or cold or pain, okay.

基本上，从皮肤到大脑的整个路径将不同于热、冷或疼痛的路径，好吧。

So, the whole, like, circuit, the anatomy, the wiring is totally different.

所以，整个电路、解剖结构、接线都是完全不同的。

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.

现在，我们正在进行的一些研究让我们感到非常兴奋，因为这再次涉及到你的问题，比如为什么它对人类如此重要和具有转化影响。

You know, we think this pathway is also important for the ability of touch to relieve stress and anxiety and depression.

你知道，我们认为这条通路对于触摸缓解压力、焦虑和抑郁的能力也很重要。

When you’re down or going through some negative emotion, just think about a hug from a loved one, a parent, a friend.

当你情绪低落或经历一些负面情绪时，想想亲人、父母、朋友的拥抱。

It can really calm you down, and make you feel better.

它确实可以让你平静下来，让你感觉更好。

We appreciate this phenomenon, but how it works at a molecular, cellular and neuronal level is almost completely unknown.

我们欣赏这种现象，但它如何在分子、细胞和神经元水平上发挥作用几乎完全未知。

The skin to brain pathway for social touch that we’ve been discovering and elucidating, we think could be important for that.

我们一直在发现和阐明的社交接触的皮肤到大脑的通路，我们认为对此可能很重要。

And we have really strong evidence.

我们有非常有力的证据。

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.

它尚未发表，但希望，你知道，也许在今年晚些时候，我们将提交这篇论文，表明激活这条通路可以缓解负面状态，这真的很令人兴奋。

And we do think it has direct therapeutic potential.

我们确实认为它具有直接的治疗潜力。

Maybe we can even think about treating diseases of the brain, chronic stress, not in the brain but by targeting neurons in the skin.

也许我们甚至可以考虑治疗大脑疾病、慢性压力，不是在大脑中，而是通过针对皮肤中的神经元来治疗。

I have to appreciate my limitations as a molecular biologist, neuroscientist.

我必须认识到自己作为分子生物学家、神经科学家的局限性。

Some of these questions may be slightly outside of the realm of where we can approach.

其中一些问题可能稍微超出了我们可以解决的范围。

One is, what a crazy thing to do.

一是，这是一件多么疯狂的事情啊。

That’s not a question.

这不是一个问题。

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?

另一个问题是，我们是否要对人类进行基因改造，以便他们能够进行蓝光疗法，作为尝试治愈某些精神疾病的一部分？

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.

但无论如何，这表明进化生物学和观察不同物种的美丽，有这种蛋白质和藻类可以让藻类穿过这些泥泞的池塘到达蓝光。

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.

它是一个离子通道，一个非选择性阳离子通道，这基本上意味着蛋白质的一部分，当蓝光照射到它时，通道打开，它允许正离子涌入表达该蛋白质的细胞。

This is, like, perfect for neurons.

这对于神经元来说是完美的。

Neurons are electrically excitable cells that fire to positive ionic current flowing into the neuron.

神经元是可电兴奋的细胞，可激发流入神经元的正离子电流。

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.

因此，如果你可以通过某种病毒基因工程将这种特殊的蛋白质放在你的神经元表面，你就可以通过这种方式赋予直接激活这些神经元的能力。

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.

因此，作为该项目的一部分，我们进行了一些基因工程，将小鼠杂交在一起，将这种蓝光敏感蛋白仅放入这些神经元中。

And we can just shine light directly to the skin, as you mentioned to confer behavior.

正如您提到的，我们可以直接将光照射到皮肤上以赋予行为。

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.

现在，要在人类身上做到这一点，人们必须达到可以进行基因工程以将这种蛋白质添加到感兴趣的细胞类型中的程度。

People are doing this now to treat – this is not our work – but to treat like forms of retinal degeneration and blindness actually.

人们现在这样做是为了治疗——这不是我们的工作——而是为了治疗类似的视网膜变性和失明。

It’s really incredible.

真是不可思议。

So maybe there is a pathway for using this technology to treat people.

所以也许有一条利用这项技术来治疗人类的途径。

So for one, they don’t feel many forms of pain, for reasons that are not fully clear.

因此，一方面，他们感觉不到多种形式的疼痛，其原因尚不完全清楚。

They seem to be immune or recalcitrant, unable to get cancer.

他们似乎具有免疫力或顽固不化，无法患上癌症。

They’re long lived for rodents, so they live about 30 to 40 years.

对于啮齿类动物来说，它们的寿命很长，因此它们的寿命约为 30 至 40 年。

And they’re highly social.

而且他们的社交能力很强。

And this is the thing that we really keyed in on my lab to date.

这是迄今为止我们在实验室中真正关注的事情。

In the last three plus years or so, we’ve been working with them.

在过去三年多的时间里，我们一直在与他们合作。

They’re actually the most social animals in the entire mammalian kingdom.

它们实际上是整个哺乳动物王国中最具社交性的动物。

So, one colony can contain dozens or hundreds of animals all living together and a really tight-knit colony.

因此，一个群体可以容纳数十或数百只动物，所有动物都生活在一起，形成一个非常紧密的群体。

And they’re driven by this really single dominant queen, who’s the matriarch that kind of guides the whole society.

他们是由一位真正的独裁女王驱动的，她是引导整个社会的女族长。

And all the other animals are essentially workers and drones and are reproductively suppressed in the presence of the queen.

所有其他动物本质上都是工蜂和雄蜂，在蜂后面前繁殖受到抑制。

She’s the only one who mates with one or two like breeding males in a colony.

她是唯一一个在群体中与一两只类似的繁殖雄性交配的动物。

And she continues to give birth her entire life.

她一生都在继续分娩。

So, no menopause or signs of slowing down.

因此，没有更年期或放缓的迹象。

And so, as she has a litter, they never leave.

因此，由于她有一窝孩子，他们永远不会离开。

The colony just gets bigger and bigger and bigger, okay.

殖民地变得越来越大，好吧。

They’ve decided that it’s best for their survival of their colony to do everything together, okay.

他们决定，为了殖民地的生存，最好一起做所有事情，好吧。

They chiefly come from East Africa, Kenya, Ethiopia.

他们主要来自东非、肯尼亚、埃塞俄比亚。

They live completely underground as well.

他们也完全生活在地下。

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.

主要的假设是，你知道，也许在这种干燥、干旱的沙漠气候中，食物和资源并不丰富，更容易有一种公共的生活方式，这样一些动物就会觅食并希望偶然发现块茎，比如红薯。

And if they do, like the whole colony is alerted and they all can feed off that together.

如果它们这样做了，就像整个殖民地都收到警报一样，它们都可以一起吃掉它。

So, you know, we want to know like, how does this pain insensitivity work?

所以，你知道，我们想知道，这种疼痛不敏感是如何发挥作用的？

How does you know this highly social life, like how is it set up?

您如何了解这种高度社交化的生活，比如它是如何建立的？

How is it maintained?

它是如何维护的？

How do they even recognize one another, especially because they’re essentially blind?

他们如何认出彼此，特别是因为他们本质上是盲人？

And from our early studies and observations, it appears that, not saying other senses are not important, but touch is certainly outsized.

从我们早期的研究和观察来看，并不是说其他​​感官不重要，但触觉确实非常重要。

You know, most of their sensory cortex seems to be dedicated to touch.

要知道，他们的大部分感觉皮层似乎都是专门负责触摸的。

So, they’ve lost the visual parts of their sensory cortex because they’re blind.

因此，他们失去了感觉皮层的视觉部分，因为他们是盲人。

But the somatosensory cortex, the touch cortex, has like encroached upon it.

但体感皮层、触觉皮层似乎已经侵占了它。

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.

所以，我们认为它们就像触觉专家，它们可能能够用触觉来做其他视觉动物用视觉做的事情。

Like communicate and recognize one another and know who it is that they’re interacting with.

喜欢沟通并认识彼此，并知道他们正在与谁互动。

We have long-term stable relationships.

我们有长期稳定的合作关系。

You know, people for 10 or 20 years, or you see a friend from college or whatever, you remember them.

你知道，10年或20年的人，或者你看到大学里的朋友或其他什么的，你会记得他们。

And these sorts of dynamic relationships that we see in their colonies we don’t see like in other animals.

我们在它们的群体中看到的这些动态关系是我们在其他动物中看不到的。

So, I think there are principles that we hope are very similar and could teach us about societies.

因此，我认为我们希望有一些非常相似的原则，并且可以教会我们有关社会的知识。

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.

你知道，我认为一个非常令人兴奋的想法是，如果我们能够学习它们用来相互合作的原理、基因、分子、神经回路、神经网络，并使用共享资源，例如，其中一些可以用来告知人类社会，以及我们如何在资源有限的情况下更好地合作。

It’s really fascinating as you mentioned, right.

正如你提到的，这真的很有趣，对吧。

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?

如果你在舒适的家中，一个所爱的人抚摸你的背或手臂，那可能感觉很好，但如果你知道你在 1 号火车或其他地方，有人这样抚摸你，对吗？

You wanna recoil, and you know it’s not gonna feel good.

你想要后坐，你知道这感觉不会很好。

But it could be the same touch to the skin.

但对皮肤的触感可能是一样的。

So then how does your brain know that this touch is in a good context and this is a bad context?

那么你的大脑如何知道这种触摸是在良好的环境中，而这是在不良的环境中呢？

There must be some sort of gating in the brain that allows you to quickly approximate how you should respond.

大脑中一定存在某种门控，可以让你快速估计出自己应该如何反应。

And how does that all work?

这一切是如何运作的？

It’s unclear, but I think we have good approaches to kind of study this.

目前还不清楚，但我认为我们有很好的方法来研究这个问题。

Those are the moments that I really live for, where we can go from not knowing to – at least at that moment – we might be the only people in the world who have appreciated something.

这些是我真正生活的时刻，在那里我们可以从不知道到——至少在那一刻——我们可能是世界上唯一欣赏某些东西的人。

Back to the mouse, I talked about those neurons we discovered as part of like that positive balance, social reward pathway.

回到老鼠，我谈到了我们发现的那些神经元，它们是积极平衡、社会奖励途径的一部分。

Now if we give animals mice that same stimulation, but we pair it, they’ve learned to associate with something negative like a shock.

现在，如果我们给动物老鼠同样的刺激，但我们将其配对，它们就会学会将诸如电击之类的负面事物联系起来。

And now we do that optogenetic stimulation to activate the neurons.

现在我们通过光遗传学刺激来激活神经元。

The animals don’t have a positive response; they have a negative response.

动物没有积极反应；他们的反应是否定的。

So, we can easily dial in, like, good touch, bad touch in the animals and read this out.

因此，我们可以轻松地输入动物的良好触摸、不良触摸并读出这些信息。

So now we’re saying, “Well, how does this look in the brain?”, okay.

所以现在我们说，“好吧，这在大脑中看起来怎么样？”，好吧。

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.

我们对大脑中的一个区域感到非常兴奋，称为眶额皮质，即额叶区域，大脑的前部，似乎整合了感觉成分和学习和计划等高级功能。

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.

我们认为，可能存在与大脑其他区域对话的神经群，让动物知道，比如动物是否处于良好的状态，触摸会被认为是好的，或者动物是否处于害怕或焦虑的地方，或者有过不好的经历，这样，现在这个喜欢积极暴力网络的大门就不会被激活。

So early days of this project, but we’re trying to figure out how this works at the level of the brain.

这个项目还处于早期阶段，但我们正在尝试弄清楚它在大脑层面是如何运作的。

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?

我想我只是想知道在这个科学层面上你认为我们可以在多大程度上解决这个非常困难的问题：为什么它感觉像某种东西？

And this is where I think folks like me, we need to be interacting with cognitive scientists, people in psychology, people in other spaces.

我认为，这就是像我这样的人，我们需要与认知科学家、心理学人士以及其他领域的人互动的地方。

There’s too much of a disconnect between neuroscience and psychology.

神经科学和心理学之间存在太多脱节。

We’re not talking to one another, you know, but we’re both studying the brain and the mind, right.

你知道，我们不是在互相交谈，但我们都在研究大脑和思想，对吧。

The neuroscientists tend to use animal models and are doing the work I talked about very mechanistic.

神经科学家倾向于使用动物模型，并且正在非常机械地进行我谈到的工作。

Whereas the psychologists are doing really beautiful work, but they’re more tapped into, you know, the human experience.

尽管心理学家所做的工作非常出色，但他们更多地利用了人类的经验。

The more we can talk to one another, I think we’ll be able to address these higher-level problems.

我们彼此交谈得越多，我想我们就能解决这些更高层次的问题。

And this is part of the institute I’m in, the Zuckerman Mind Brain Behavior Institute.

这是我所在的研究所的一部分，祖克曼心脑行为研究所。

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.

也许这是我们研究所的一个插件，但你知道，这是我们尝试做的事情，因为这是我们通过将跨技能思考的人们聚集在一起来解决大脑和思想问题的唯一方法。

So one is just discovery, okay?

所以一个只是发现，好吗？

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?

当我们有那种恍然大悟的时刻，那种顿悟的时刻，我们会说：“天哪，就是这样了。”例如，我们都感到非常兴奋的事情是哺乳动物的哺乳，对吧？

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.

现在，我们很早就知道，例如，在哺乳时，孩子到妈妈或小狗到妈妈的皮肤上会产生吸吮刺激，而这种物理吸吮刺激足以调节乳汁的释放。

There’s like this neuroendocrine reflex that goes from the skin up to the brain back to the tissue.

就像这种神经内分泌反射从皮肤到大脑再到组织。

The milk comes down.

奶水就下来了。

The baby, the pup gets it.

宝宝，小狗明白了。

It all is initiated by, in part by touch, okay?

这一切都是由触摸引发的，好吗？

But we had no idea, like what are the touch neurons that mediate that?

但我们不知道介导这种作用的触觉神经元是什么？

In the last few months, we’ve been able to discover and put in a molecular handle.

在过去的几个月里，我们已经能够发现并安装一个分子手柄。

We found the neurons that mediate this.

我们发现了介导这一过程的神经元。

When we made this discovery, it was just like jumping for joy.

当我们有了这个发现时，我们简直高兴得跳了起来。

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.

这就像我们和其他人一直在寻找的东西，就像我们破解了它一样，数据看起来如此美丽和令人信服。

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.

就像，那些是我真正生活的时刻，在那里我们可以从不知道到——至少在那一刻——我们可能是世界上唯一喜欢某些东西的人。

Those are the moments that we live for.

这些就是我们为之而活的时刻。

So, discovery is the thing that really drives me and brings joy to my life.

所以，发现才是真正驱动我并给我的生活带来欢乐的事情。

And mentorship, right?

还有指导，对吧？

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.

帮助人们实现生活中的梦想和目标，并与他们一起工作，我也为此而活，有时这对我来说就像发现一样令人兴奋。

I mean, is that why you were smiling when he said that?

我是说，这就是他说这句话时你微笑的原因吗？

Anyway, wonderful stuff.

不管怎样，很棒的东西。

I’ll give you a hug next time I see you.

下次见到你时我会给你一个拥抱。

The Joy of Why is produced by PRX Productions.

《为什么的喜悦》由 PRX Productions 制作。

The production team is Caitlin Faulds, Jade Abdul-Malik, Genevieve Sponsler, and Merritt Jacob.

制作团队包括 Caitlin Faulds、Jade Abdul-Malik、Genevieve Sponsler 和 Merritt Jacob。

The Executive Producer of PRX Productions is Jocelyn Gonzales.

PRX Productions 的执行制片人是 Jocelyn Gonzales。

Edwin Ochoa is our project manager.

埃德温·奥乔亚是我们的项目经理。

From Quanta Magazine , Simon Frantz and Samir Patel provided editorial guidance, with support from Samuel Velasco, Simone Barr, and Michael Kanyongolo.

《Quanta》杂志的 Simon Frantz 和 Samir Patel 提供了编辑指导，并得到了 Samuel Velasco、Simone Barr 和 Michael Kanyongolo 的支持。

Samir Patel is Quanta’s Editor-in-Chief.

萨米尔·帕特尔 (Samir Patel) 是广达的主编。

The episode art is by Chanelle Nibbelink and our logo is by Jaki King and Kristina Armitage.

剧集艺术由 Chanelle Nibbelink 创作，我们的徽标由 Jaki King 和 Kristina Armitage 创作。

Special thanks to Garth Avery at the Cornell Broadcast Studio.

特别感谢康奈尔广播工作室的 Garth Avery。

I’m your host, Janna Levin.

我是你们的主持人，詹娜·莱文。

If you have any questions or comments, please email us at [email protected] .

如果您有任何问题或意见，请发送电子邮件至 [email protected]。

Thanks for listening!

感谢您的聆听！

Get highlights of the most important news delivered to your email inbox

获取发送到您的电子邮件收件箱的最重要新闻的摘要

Quanta Magazine moderates comments to facilitate an informed, substantive, civil conversation.

《Quanta》杂志对评论进行审核，以促进知情、实质性、文明的对话。

Abusive, profane, self-promotional, misleading, incoherent or off-topic comments will be rejected.

辱骂、亵渎、自我推销、误导、语无伦次或偏离主题的评论将被拒绝。

Moderators are staffed during regular business hours (New York time) and can only accept comments written in English.

版主在正常工作时间（纽约时间）有工作人员，并且只能接受英文评论。