Itch hunt

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Everyone itches.

You get a sunburn, a bug bite, even a little stray hair on your shoulder.

It's enough to make you itch.

You'll probably feel itchier than usual just by listening to this episode because it's also contagious.

Itch is usually something that we can just scratch away, but for lots of people, it's more than an annoying feeling.

If you have eczema, your skin is already inflamed, you have intense itching, more itching causes more scratching, more inflammation, more damage, more itching.

That's Brian Kim, a dermatologist.

And yes, Brian, I do.

I have eczema, which has meant some sleepless nights and wounds on my body that I scratch open and won't let heal because the itch doesn't go away.

I've tried going to doctors who've prescribed me creams and ointments.

I've tried changing my diet.

I've tried bathing in diluted bleach, which sounds crazy, but it's a thing.

And some of these things help, but not for long.

I don't need need science to tell me that there's no cure-all for itch.

I already know.

And it's not because I haven't tried to figure it out.

What I didn't know was how little scientists understood about itch at all.

10 years ago, no one cared about itch.

It's just amazing.

It's really come a long ways.

When we first started studying itch, I thought that all it was telling us was how do we sense something outside of our body.

But what it's telling us is that it's teaching us how we sense everything, not just outside of our body, not just the five senses, but a thousand senses.

I'm Manning Want, and this is Unexplainable.

Brian's a dermatologist, but he was trained as an immunologist.

His specialty was the immune system.

So when he started studying itch, people said a lot of different things.

A lot of people said, well, itch is not a disease.

It's not important.

It's not solvable.

Oh, you should just study pain.

It's more important.

Even the cynical, like, you can't make any money in itch, right?

Like, you're not going to get funded.

People have been saying stuff like this forever, because for a long time, scientists fundamentally misunderstood itch.

Itch actually is considered, or was considered, a mild form of pain.

And the idea there was that if we just studied pain better, we could actually solve the problem of itch.

But it hasn't worked out that way.

We've had pain centers in clinical hospitals and clinics all over the country, but you never heard of really about itch centers or itch specialties, right, in medicine, despite being such a common experience and symptom.

You can kind of understand how itch and pain were lumped together for so long, because they're both pretty unpleasant feelings.

And they come from the same place, our sensory nervous system, specifically the part that lets us feel touch, things like temperature and pressure, pain.

You have your skin, which is kind of the barrier to the outside world.

And into the skin are nerve fibers that go in and they act like little electrical cables that go back to your spinal cord.

And then there's a series of circuits that work its way up into the brain.

Anytime we touch something, it triggers a specific receptor at the end of these nerves and sends an electrical signal down them.

So cold triggers the cold receptor, hot triggers the hot one, and pain triggers the one for pain.

And for a long time, scientists thought that there was no dedicated itch receptor, no dedicated nerve.

We just thought that things that made us itchy also triggered their pain receptors.

But in 2007, that changed entirely.

A guy named Zhufeng Chen,

who became my colleague later, had discovered the first bona fide itch receptor in the spinal cord.

In other words, the itch highway.

What that really meant to us was that actually now this is not pain.

This is its own defined entity that's separate from pain.

And that totally changed the way everyone thought about itch, including myself.

Once itch was recognized as a unique feeling with its own dedicated receptor and pathways in the body, it became something scientists could work with.

A major effort on our part was to develop drugs that actually target itching very directly.

The idea was that these drugs could directly block off itch receptors and stop the itch signal from reaching the brain.

But treating itch turned out to be more complicated than it seemed, because there isn't just one kind of itch receptor.

Scientists have found a bunch of them.

Additional pathways beyond the first itch receptor have been identified.

Across different families, they actually have different flavors.

These different families of receptors are triggered by different things.

The most well-known are probably those itch receptors triggered by histamine molecules, which are molecules released by your immune system.

And they're partly why inflammation and allergies can make you itchy.

But that's just one flavor of itch.

If you actually look at the science, there are so many different molecules that cause itch.

Itch is probably many, many different sensations.

It could be anywhere from dozens to maybe hundred sensations, we think.

For example, some bacteria can cause itch, like one called Staph aureus.

People with eczema have way more of this bacteria on their skin than other people do.

Isaac Chu's group at Harvard discovered that bacteria trigger these itch nerves.

And I thought, wow, that's interesting.

Why are they directly sensing bacteria?

And things like pollen, dust mites, animal fur, these can also trigger itch nerves instead of just creating inflammation.

Nico Gardenzio at NCERM and Carrie Sokol at MGH detected that allergens trigger itching directly.

It's like, wow, I'm in the allergy field.

I'm a dermatologist.

I thought the immune system detected allergens, not the nerve.

I thought the whole thing was you had a hypersensitivity to peanut, not that your nerve detects peanut first.

Whoa.

I was like, this is a total flip of the script on food allergy.

This is flipping the script on how I think about asthma.

Everything I was told as an immunologist is now thrown in, not thrown into question, but at minimum, saying we need to revisit this.

You know,

we didn't know this guy was at the party all along.

A lot of these advances are only from the last few years.

There are so many more pathways itch could take than scientists originally thought.

Itch science was having its renaissance, and something clicked for Brian.

One day I realized, oh my gosh, itch is way more important than even itch.

In 2019, Brian came across a paper that mapped out a bunch of sensory nerves in the body.

These are nerves that connect our brains to our inner organs, like the lung, the stomach, the gut.

And they looked a lot like the itch nerves that he had been studying.

Those nerves that go to the skin, what we call the cell bodies or the brain of those nerves, reside really close to your spinal cord.

Okay, they're housed in this, what we call ganglia, that kind of the headquarters.

But housed within those same compartments are other nerves that go to every organ inside your body.

Not to your skin, but inside your body.

And a lot of those nerves actually have machinery that are shared with these itch nerves.

The itch nerves and molecules that Brian had become so familiar with on the skin were in all these other organs.

But why are there these nerves that go to your lung, your liver, your lymph node, your spleen,

your colon that actually look like itch nerves?

Itch might be more than skin deep.

That's next.

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This month on Explain It To Me, we're talking about all things wellness.

We spend nearly $2 trillion on things that are supposed to make us well: collagen smoothies and cold plunges, Pilates classes, and fitness trackers.

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That's this month on Explain It To Me, presented by Pureleaf.

In the last few decades, scientists have learned that the infrastructure of itch is way more extensive than we thought.

And Brian Kim thinks that itch could tell us about way more than just our skin.

Itch is the tip of the iceberg in explaining to us how we sense inflammation, how we now react to inflammation.

And then it's also telling us how do we sense allergens, how do we sense bacteria, how much of my brain, unconsciously, unbeknownst to me, is constantly sensing things throughout my body.

Scientists have found nerves and receptors threading our internal organs that look a lot like the ones on our skin.

So then you say, why are these nerves so similar to the nerves that go to the skin?

Yeah,

why are they so similar?

Do we know what they're doing?

We know a little bit.

A lot of it is a question mark because this is where the frontier emerges.

So there are nerves that have a very distinct identity.

So nerves that have, for instance, touch quality are very, very distinct.

Actually, even structurally are different.

But these nerves are kind of within the family of just these really slow sensory nerves.

And then you layer on the fact that they sometimes have molecules or receptors that we know causes itch in the skin.

So you say, oh, well, if that causes itch in the skin, what does it do in the gut?

And we thought, well, those organs don't itch,

but they must be doing something unique that may mimic itch in some way.

And it's kind of a wild thought.

Yeah, what do you mean by mimic itch?

Do I think that your lymph node itches?

No.

Do I think you scratch your lymph node?

No, I don't really think that either.

Okay.

But now when you get to the lung, you start to make sense of it.

You say, well, you know, there are these reflexes in the lung that mimic itching and scratching, mechanical reflexes to expel,

like coughing, or in the upper air race, like sneezing.

And then if you go to the gut, there are things that mimic itching.

Like, if you get diarrhea, it's an expulsion event.

You have motility, just like you're scratching.

What is motility exactly?

Movement.

Your gut will actually kind of oscillate and move to try to move food or stool, right, down.

So, that's essentially a form of the gut scratching.

Oh, and what we learn from itch is that every sensation

also requires a reflex movement, right?

Like a reaction.

A reaction, exactly.

Every action requires a reaction or whatever that term is, right?

So, so that motif is not limited to itch.

So you're saying that we can think of itch kind of like a template

to like understand how other organs sense and react to things.

Yeah, yeah, exactly.

That's a simple way to put it.

Maybe the body just said, hey, itch is all over the skin.

So many molecules can cause itch.

It's important at a population level, but maybe we can now use this in other ways to get rid of urine properly, get rid of stool properly, get rid of phlegm from the airway properly, help you to sneeze so you don't get infected with the virus.

But there's another layer there.

Those are simply mechanical reflexes.

But what itch has told us is that it actually also has another reflex in there that goes beyond the mechanical.

What do you mean?

So let's use itch as an analogy.

You have a fleeting itch and you scratch, you cause inflammation in your skin,

but then the inflammation, if you're a healthy individual, the inflammation goes away.

How does it go away?

What is that reaction that helps you resolve that?

Well, you could think about almost every physiology in the body in these terms.

How does any event know how to shut off in the body?

Because your body senses that event and knows to shut it off.

And that is the frontier of the biology.

So, in other words, if you get an infection, your immune system fights it off.

But what we're saying is that also your nervous system has to sense that infection to actually help your immune system shut it off in the right way and say, hey, we sensed it.

Here's our reaction.

We're going to help you react to it, shut it out, back to health.

And now we can understand how, if such sensations or reactions to those sensations become perturbed, how this could lead to disease.

So,

I mean, I guess if we could better understand what these itch-like nerves are doing, then what could this lead to?

I think it could get further than even what we just discussed.

So itch basically is a template for, in my mind, of now understanding lots of different kinds of sensation that are much more even lofty than itch in some ways.

If you say the tip of the itch iceberg is now going to tell us how we understand diseases that are irritating

and

involved in kind of irritating sensations that make you want to expel things from the body or just irritate you a lot, like interstitial cystitis of the bladder, irritable bowel syndrome, chronic coughing,

you know, gastritis, esophageal reflux disease, all these things that are irritating, that have no treatments.

People don't even think about it as a sensation.

That's a big frontier.

Have we definitively proven that there is this incredible symphony across all these diseases?

Absolutely not.

Okay.

If we did, it would not be a frontier.

It would be a busy, busy intersection of many people.

I anticipate fully, though, that that is what's going to happen in the next 10 years.

Itch science has come a long way, and it has more to go.

What Brian's excited about is the potential that it has to help us understand all kinds of other sensations and diseases.

But for me, learning about itch itself has made this eczema stuff feel a little easier.

Like, maybe the creams and the diets and the baths I did weren't fully working because they weren't targeting the right pathways.

Or maybe the itch was caused by more than one thing.

I don't know yet.

But the science of itch is giving me hope that, if not today, there will eventually be a treatment that works for me.

And that anybody with itch might be able to find the relief that they need.

This episode was reported and produced by me, Man Ning Wen.

We had editing from Jorge Jess with help from Brian Resnick, sound design and mixing from Christian Ayala, music from Noam Hasenfeld, fact-checking from Melissa Hirsch, and Meredith Hodnott runs the show.

Bird Pinkerton turned to the platypus and told her about the octopuses.

She told them about the attack.

She told them about everything.

They turned to her and said,

We narrow.

Special thanks to Li Wen Dang, Gil Yasapovich, Taylor Sheehan, and Heidi Kong.

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