An itching paradox – a molecule that triggers the urge to scratch also turns down inflammation in the skin
Itching can be uncomfortable, but it’s a normal part of your skin’s immune response to external threats. When you’re itching from an encounter with poison ivy or mosquitoes, consider that your urge to scratch may have evolved to get you to swat away disease-carrying pests.
But, paradoxically, some of the mechanisms behind this feedback loop also stop inflammation from getting worse. In our newly published research, my team of immunologists and neuroscientists and I discovered that a specific type of itch-sensing neuron can push back on the itch-scratch-inflammation cycle in the presence of a small protein. This protein, called interleukin-31, or IL-31, is typically involved in triggering itching.
This negative feedback loop – like the vicious cycle – is only possible because the itch-sensing nerve endings in your skin are closely intertwined with the millions of cells that make up your skin’s immune system.
IL-31 is rarely present in the skin or blood of people who don’t have a history of eczema, allergies, asthma or related conditions. But those with conditions like eczema that cause chronic itch have significantly increased skin production of IL-31. There is strong evidence that IL-31 is one of a small set of proteins that immune cells produce that can bind directly to sensory neurons and trigger itching. Small amounts of purified IL-31 injected directly into skin or spinal fluid leads to impressively rapid-onset itching and scratching.
However, when my colleagues and I induced rashes in mice by exposing them to dust mites, we found that itch-sensing neurons turned down the dial on inflammation at the site of itching instead of promoting it. They did so by secreting small molecules called neuropeptides that, in this context, directed immune cells to respond less enthusiastically. In sum, we had discovered an inverse relationship between itching and skin inflammation, tethered by a single molecule.