Why we scratch an itch

Scientists in the United States say they have unpicked the real purpose of scratching an itch: scratching activates pain nerves, which turn off itch nerves but turn on immune defences in the region of the irritation. The resulting feedback loop is thought to have evolved to protect us against infections. Here’s Daniel Kaplan at the University of Pittsburgh…

Daniel - Cells of the immune system can release small molecules that are responsible for triggering some of our sensations, like painful sensation or itch sensation. A number of years ago, we looked at a type of neuron that encodes pain sensation and found that if we just activate these neurons by themselves, that's more than enough to trigger all kinds of inflammation in the skin. So we were curious to continue that kind of work and look whether something similar happened with neurons that encode itch sensation.

Chris - That's intriguing. So when you activate the pain nerve, it also then turns on immune responses, is what you're saying, and you're wondering, well, what about itch then? Does an itch turn on an immune response as well?

Daniel - That's exactly right. What we found though is that activating the neuron itself didn't seem to trigger any inflammation. Rather, what happens is that when the neurons that encode itch sensation are activated, you get the expected result, which is the mice start to scratch. But the unexpected finding was that it was the act of scratching that was actually required for inflammation in a number of different models of eczema.

Chris - That's very interesting. So there are specific nerves that just tell your body, this patch of skin itches, and there are another class of nerves that say this patch of skin hurts. But when you activate the itch ones, you feel an itch, but you don't get an immune response. You activate the pain ones and you do get an immune response.

Daniel - That seems to be true, at least as far as we've been able to determine.

Chris - And so your hypothesis is, well, when I itch, I scratch, the scratch causes some pain and the pain causes some inflammation.

Daniel - Well, that's actually what we discovered, is that the act of scratching ends up activating these pain sensing neurons, and that then leads to inflammation in the skin. So in that sense, by scratching, it actually sort of completes this circuit such that now you get nerve-driven inflammation to something that otherwise wouldn't cause pain.

Chris - What cells are actually releasing the immune effectors then, these responses, these signals that you're saying you get when you evoke pain and it produces an immune response? Where's that coming from? What's the circuitry there?

Daniel - We know there are a number of these small molecules that are released from the neurons, and some of them can trigger a type of cell in the skin called a mast cell. These cells have a lot of pre-made chemicals in them, and when they're activated, these chemicals get released into the skin, and that leads to inflammation that's important for the response to bacteria.

Chris - Mast cells are jam-packed with histamine, aren't they? Because when we have an allergic reaction, you get a histamine response, and that causes swelling and itching. So doesn't this feed back on itself then? If you've got a cell that releases something that makes you itchy and it was the itch that made you scratch in the first place, doesn't this mean you end up scratching yourself to death?

Daniel - That's absolutely correct. So when you have scratching, the mast cells are activated, this does release histamine, the histamine then acts on receptors which are on these itch-sensing neurons, and you get then more itch. This is one of the reasons why we have this phenomenon called the itch-scratch cycle. So if you scratch an itchy area or a rash, it feels very good, but then a few minutes later, it itches significantly more, and that's part of this positive feedback loop that gets developed.

Chris - In one respect then, that's a good thing, because if you're detonating immune responses and inflammatory chemicals from your mast cells like this, that's going to put the immune system on high alert. So if, say, a mosquito or something, we're trying to drill holes in your skin, you've been alerted to the fact that that patch of skin is not in a good way to pay attention to it. But that also sounds like it could have negative impact, because if you have this itch-scratch cycle, what breaks the cycle? Because otherwise, you would literally dig holes in your skin, wouldn't you?

Daniel - Well, this is part of the paradox of scratching. So on the one hand, scratching alerts you to something that needs to be removed from the skin, and from our findings that the scratching by activating these pain-sensing neurons, triggering inflammation, has a very important role in limiting bacterial infections at that site. But at the same time, it makes the rash a lot worse. So in general, we scratch an itch, and it often feels pleasurable, this common sensation. However, we will scratch an itch until it starts to hurt, and that's usually the trigger to stop scratching. So that's one of the ways in which the itch-scratching cycle can be broken in a short time scale. But for many people, this itch-scratch cycle becomes quite a problem and requires medical intervention.

Chris - So that would be someone with eczema or something like that, acute dermatitis?

Daniel - Yeah, precisely. And there are many forms of dermatitis, and the scratching is well known to make the eczema rash significantly worse, oftentimes to the point of needing a visit to your dermatologist to help you sort it all out.

Chris - Presumably then, a better understanding of this sort of wiring that's going on, as well as the interaction with the immune system that you've uncovered with this, that does give us some possible new insights into ways that we might be able to better manage things like dermatitis.

Daniel - Yeah, that's absolutely correct. In fact, previous research from a number of other people have found that the molecules released by the types of immune cells that are associated with allergy can themselves cause itch. And in fact, there are a number of new medications that target those molecules, which have been incredibly helpful.