Researchers at the University of Michigan have discovered a previously unknown biological pathway that explains how certain touch-sensitive hairs cause the sensation of itching. This finding, obtained in a mouse model, reveals a dedicated sensory system that may ultimately help scientists develop better treatments for chronic itch disorders.
“Itching is one of the main symptoms of most patients with chronic skin inflammation,” says Bo Duan, associate professor in the Department of Molecular, Cellular, and Developmental Biology. “What we discovered is a pathway that appears to play a very important role in both acute and chronic itch.”
Researchers have identified a previously unknown type of hair called vellus hair in mice and a group of specialized touch-sensing neurons connected to it. These hairs resemble the thin, short, light-colored vellus hairs that cover most of the human body and are commonly known as peach fuzz.
This research was supported in part by the National Institutes of Health and was published in the journal neuron.
Hidden nerve cells are associated with chronic itch
To investigate the role of these neurons, the research team studied mice with chronic skin inflammation comparable to eczema in humans. Mice with specialized neurons scratched normally in response to itch. But in animals lacking these neurons, or in which the neurons were switched off, scratching behavior was dramatically reduced.
Current treatments are fairly effective against chemical itch caused by irritants such as mosquito bites and poison ivy. They are far less effective against persistent itching associated with chronic skin inflammation. The newly identified “mechanical itch” pathway could provide an entirely new target for future treatments, Duan said.
“If we want to treat chronic itch, we need new pathways to target,” Duan said. “And our study suggests that this population of neurons could be targeted in the future. We have ongoing projects examining this.”
Although researchers cannot directly test the same pathway in humans, some evidence suggests humans may have a similar system. For example, humans have the genes necessary to produce these specialized touch-sensing neurons.
The researchers also identified a protein in mice that transmits itch signals from the hair to the spinal cord via these neurons. When human neurons grown in laboratory cultures were exposed to the same protein, they showed a similar response.
“Our study shows that humans may have a similar mechanical itch transmission mechanism,” Duan said. “We also found that the body has a system dedicated to this type of sensation.”
Why peach fluff causes itching
One of Duan’s favorite classroom demonstrations helps explain this phenomenon.
Curl one corner of the tissue into a long strip and gently brush away the small hairs around your lips. If you lightly touch the thin, soft hair, rather than the thick terminal hair, you may suddenly feel itching.
“Humans and animals both experience this type of itch, but no one knew the molecular and cellular mechanisms behind it,” Duan said.
New discoveries have identified the sensory pathways that connect these specialized hairs to the nervous system. Combined with the research team’s previous work, this study provides a clearer picture of how mechanical itch signals travel through the body.
Solving a century-old mystery
Scientists have described for the first time a rare vellus-like hair found in mice more than 100 years ago. These hairs are especially common behind the ears, under the lips, and near the base of the feet. Despite its early discovery, it has received relatively little attention from sensory researchers.
There was no established way to study this type of itch in mice, so Duan’s team had to develop their own experimental approach.
“You can’t say rats are itchy,” Duan said. “But it will hurt.”
The researchers used small loops of thread to gently stimulate the animals’ vellus-like hairs to induce mechanical itch. After identifying the neurons responsible for the response, they genetically modified those cells so that they could be activated by blue light. Simply exposing mice to blue light triggered the same scratching behavior seen during mechanical stimulation, providing strong evidence that these neurons directly generate the itch sensation.
Why we don’t always feel itchy
Peach fuzz and similar hairs are especially abundant around the mouth and ears of both humans and mice. Duan suspects that these hairs may have evolved as an early warning system to alert mammals when insects or parasites come into contact with sensitive areas of their bodies.
Although humans are covered in vellus hair (with notable exceptions such as the palms of our hands), we don’t always scratch. Previous research by Duan’s lab offers one possible explanation. The spinal cord contains “gating” circuits that normally suppress mechanical itch signals, allowing them to pass only under certain conditions.
Understanding how this hidden sensory system works could ultimately help researchers design new treatments for chronic itch, especially for patients with inflammatory skin diseases whose symptoms remain difficult to control with existing drugs.
