Researchers have discovered why a touch can cause such severe itching in mice and, in the process, identified some possible therapeutic targets.
For some people, particularly those who are elderly, even a light touch of the skin or contact with clothing can lead to unbearable itching. What’s worse, anti-itch treatments, including hydrocortisone, don’t provide much relief.
The new research, which appears in the journal Science, indicates that itching resulting from touch is directly related to the number of touch receptors embedded in the skin. The fewer the receptors, the more likely it is that touching will induce itching.
“Itching caused by touch becomes more common as we age and is especially problematic for people with dry skin or who already suffer from chronic itching,” says senior investigator Hongzhen Hu, an associate professor of anesthesiology who conducts research as part of the Center for the Study of Itch at Washington University in St. Louis. “It can be more than a nuisance, and there are no drugs available to treat this type of itching, so we wanted to identify the underlying causes in hopes of finding better ways to treat it.”
Hear Hu explain the findings:
Studying mice, the scientists discovered that the number of touch receptors called Merkel cells in the skin declined as the animals aged. They also found fewer of these touch receptors in animals with dry skin. Not having as many Merkel cells made itch problems more likely when the animals were poked with a hair-like nylon device that scientists use to study itch responses.
“As the number of Merkel cells went down, problems with touch-related itch went up,” Hu says. “What exactly Merkel cells do has not been clear, but our findings suggest they help control the itch response. When you lose these cells, their ability to inhibit itch also is lost.”
In additional work, the researchers turned to genetically engineered mice whose Merkel cells they could activate with a chemical compound. When they gave the compound to the animals, they were less likely to scratch when researchers touched them with the hair-like device.
“This gives us hope that if we can control the activity of the Merkel cells themselves, we may be able to control this type of itching,” says first author Jing Feng, a postdoctoral fellow at the School of Medicine.
The researchers also identified a second potential therapeutic target—a protein on the Merkel cells that appears to control itch. The protein, called Piezo2, is made on the membranes of the cells. In the mouse experiments, the researchers found that the Piezo2 protein played a role in controlling Merkel cells as they tamped down itch.
Hu and Feng are now analyzing skin samples from patients suffering from touch-related itch problems. Brian S. Kim, an assistant professor of medicine and co-director of the Center for the Study of Itch, treated those patients.
“As people age, their skin changes, and for some people this can lead to severe, intractable itching,” Kim says. “For example, many of my patients with severe, chronic itch associated with aging cannot tolerate certain types of clothing. That observation fits with Dr. Hu’s findings that these receptors in the skin suppress itch, but with aging, the cells disappear, and normal touch sensations can be perceived by some patients as pathologic itch.”
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If the skin biopsy samples from Kim’s patients show that they have depleted numbers of Merkel cells, activating such cells in patients may help relieve itching the same way it did for mice in the study.
The National Institute of General Medical Sciences, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health (NIH) supported this work.
