Hi and welcome to the A16Z podcast. I'm Hannah. In this episode, we talk all about the biology of pain with Clifford Wolf, professor of neurobiology at Harvard Medical School, who has dedicated his career to the subject. The conversation covers everything you ever wondered about the nature of pain, from why we even feel it and what the biological purpose of pain is, to whether or not all

pain is the same, or if some kinds of pain function differently, feel different, have different

purposes, or even if some people feel pain differently from others. Wolf describes the four

different broad types of pain we experience, what the purpose of each one is, what it means now

that we can phenotype different

kinds of pain and begin to understand them as distinct and different from each other, and how technology

is enabling this new, deeper, and much more complex understanding of the nature of pain. We also talk about

what the biological link between pain and addiction really is, plus the one thing

you might do that we know makes your experience of pain worse. You've been working on the subject

of pain for your entire career. What drew you to that subject to begin with? What was it that

first sparked that initial interest for you and where you began investigating? When I was a medical

student, I was on the surgical ward, and at that time, there was

minimal treatment for post-operative pain. So I came into the ward, and there were a group

of patients who had had major surgery, and all of them were in severe discomfort. And I said to the attending a surgeon, what are you doing? Why, why aren't you treating them with pain? He looked at me as if I was crazy and he said, they've just had surgery. What do you expect? They were in pain. Even the idea of treating the pain was not. Absolutely. It was just thought, you have surgery, have pain, and then you put up with it

until the pain goes. And I just thought to myself, that doesn't sound right. At that time, there was

very little understanding of the mechanisms of pain and indeed very few treatment options. Now as we have

much greater understanding, but unfortunately, the treatment options haven't really expanded,

and they are also accompanied by undesired effects, particularly in the case of the opioids.

So let's talk a little bit about what the understanding looked like then and what it's beginning to look like now.

So what was our understanding of the

mechanism of pain back then when we just sort of assumed, okay, you have surgery, you're in pain.

At that time, I just thought that all pain is similar, that you either have no pain or you have

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