Neuroscientists Hack Itching, Exposing a Mysterious Neural Circuit

Scratching an itch doesn't take a whole lot of brain horsepower. It's not automated in the same sense that breathing and heart beating are, but when it comes to everyday itch-scratching it might as well be. The brain registers itching—via the same pathways that transport sensations like temperature and pain from the skin—and it naturally responds by deploying fingernails. The itch is scratched, and that feels good.

Actually, scratching an itch feels more than good. As someone that suffers from chronic eczema and spends a disproportionate amount of time in contact with poison oak, I'm something of a connoisseur of scratching and its unique, fleeting gratification. I'm a lot like a dog, if we're being honest. I love a good scratch.

There's more to itch scratching than one might imagine, at least from a neuroscientific perspective. It's only been in recent years that we've started to isolate and identify that actual neural circuitry responsible for itching. The first identification of a nerve in the skin—any nerve—responsible for the itch sensation came in 1997. Now, researchers from the Chinese Academy of Sciences have successfully identified a neural circuit in the brain that's thought to service this elusive sensation—a major advance. Their work is described this week in Science.

A not very well understood part of the brain associated with pain and other visceral sensations is known as the parabrachial nucleus (PBN). It serves as a sort of relay station for signals related to all kinds of happenings in the body and by tweaking neurons here it's possible to trick the brain into doing some interesting things, such as switching off hunger.

The researchers behind the current paper were interested in a bundle of neural receptors called GRPR, which project into the PBN from the spine. It was discovered in 2007 that the GRPR neurons are responsible for passing along itch signals into the brain. Because there are lot of different sorts of spinal neurons that project into the PBN, the Chinese team hypothesized that this is where the key itch connection between the body and brain lies.

Testing out this hypothesis involved mice outfitted with glowing fluorescent nerve cells, a technique broadly known as optogenetics. Basically, it allows researchers to watch neurons in action. As nerves start firing, they light up.

Putting this together with tiny injections of histamine to trigger itching sensations demonstrated the relationship between the itch sensation and the PBN, which did indeed light up as the mice were made to itch. The hypothesis was further tested by using designer drugs to limit PBN functioning, which resulted in less scratching reflexes in mice made to itch via histamine injection.

"Our findings suggest that the PBN represents a first central relay for itch sensation, and its activity regulates both acute and chronic itch–induced scratching," the authors conclude.

This is far from a trivial finding. Yes, itching is weird, but for many people, itching can become a debilitating condition when it occurs chronically without any real trigger, a condition known as neuropathic itch or neuropathic pruritus. At its worst, it sounds like actual hell on Earth. If you haven't read Atul Gawande's New Yorker story "The Itch," go do that right now. In it, Gawande notes that Dante made itching a key feature of the Inferno (hell): "Then I saw these two scratch themselves with nails/ Over and over because of the burning rage/ Of the fierce itching which nothing could relieve."