Link between vellus-like hairs and chronic itch identified in mouse model

Photo by Svdmolen via Wikimedia Commons

Working with mouse models, research led by the University of Michigan has revealed previously hidden biology of how touch-sensitive hairs create itching sensations. This fundamental discovery opens new avenues for better understanding and potentially addressing human health conditions characterized by persistent itchiness.

The work, supported in part by funding from the National Institutes of Health, was published in the journal Neuron.

“Itch is one of the major symptoms in most chronic skin inflammation patients,” said the study’s senior author Bo Duan, PhD, in a press release. “What we’ve discovered is a pathway that we believe plays a very important role for both acute and chronic itch sensation.”

Dr. Duan is an associate professor in the Department of Molecular, Cellular, and Developmental Biology at the university.

The team discovered a previously unrecognized class of hairs in mice, known as vellus-like hairs, and a specialized population of touch-sensitive neurons that connect to them. As their name suggests, these hairs are similar to the fine, short, light-coloured vellus hairs found on humans.

For one set of experiments, the team worked with mice that had chronic skin inflammation, comparable to atopic dermatitis in humans. Mice expressing the identified touch-sensitive neurons scratched normally, as expected. But in mice lacking those neurons or in which the neurons were inactive, the itching response was greatly reduced.

While there are several ways to help soothe chemical itch caused by things like mosquito bites and poison ivy, those treatments are ineffective against itch caused by skin inflammation, Dr. Duan said. This study suggests that treatments targeting the “mechanical itch” pathway could be more successful.

“We need a new pathway to target if we want to treat chronic itch,” Dr. Duan said. “And our research suggests that this population of neurons could be a target in the future. We have ongoing projects looking at this.”

Although the team can’t run experiments to identify the same or related pathways in humans directly, the researchers are already building the case with other forms of evidence. For starters, humans do possess genes required to make these touch-sensitive neurons.

The team also discovered proteins in mice that help transmit the itch signal from hairs to the spinal cord via the specialized neurons. Human neurons grown in cultures respond to the same proteins, the team found.

“Our study indicates that humans may have this same kind of mechanism to transmit mechanical itch,” Dr. Duan said. “It also reveals that the body has a dedicated system for this type of sensation.”

For the new study, the team mechanically stimulated itch in mice using a small loop of thread and stroking the animal’s vellus-like hairs. Once they identified the neurons that gave rise to the itching response, the researchers could then make those neurons sensitive to blue light. Shining light on a mouse’s skin and observing it scratch in the same way it did with mechanical stimulation helped confirm the specific neurons’ role in itch.

Vellus and vellus-like hairs grow in higher numbers near human and mice mouths and ears, Dr. Duan said. This suggests they may have evolved as a warning system for mammals to alert them when pests or parasites are trying to get in.

But human bodies are covered in vellus hair (with notable exceptions, such as the palms of our hands), which raises the question of why humans are not constantly scratching if they are covered with such sensitive touch receptors. Another one of Dr. Duan’s earlier projects studying itch in mice could also explain that: Within the spinal cord, there are “gating” circuits at work that essentially block the mechanical itch signal unless it’s activated in a particular way.