Getting old can be a real itch. In addition to having memory and muscle loss, many elderly people develop supersensitive skin that gets itchy at the lightest touch. Scientists don’t know what causes this miserable condition, called alloknesis, or how to treat it. Now, however, a study in mice has revealed a counterintuitive mechanism for the disorder: a loss of pressure-sensing cells in the skin. Although the findings have yet to be replicated in humans, the study raises the possibility that boosting the function of these cells could treat chronic itch in people, both young and old.
Chronic itch is different from chemical itch, which occurs when the immune system reacts to a foreign substance, such as oil from a poison oak leaf or saliva in a mosquito bite. Instead, chronic—or mechanical—itch is usually triggered by light pressure, such as the brush of fibers from a sweater. The condition is maddening, and when people repeatedly scratch their fragile, dry skin, it can lead to major health problems, including infections, says study author Hongzhen Hu, an anesthesiology researcher at the Washington University School of Medicine in St. Louis, Missouri.
Like people, mice visibly itch more with age. To find out why, Hu and colleagues used a hair-thin nylon filament to apply a precise amount of pressure to a patch of shaved skin on young and old rodents’ necks. Young mice didn’t respond much to the gentle touch, but the older mice scratched furiously at the spot. Analyzing skin samples from mice of both ages, the team found that older mice had far fewer pressure-sensing Merkel cells than young mice did. The fewer Merkel cells a mouse had, the more their touch-related itch problems increased in response to the filament, the researchers report today in Science.
Next, the team tested how young mice genetically engineered to lack Merkel cells would respond to the nylon fiber. They scratched with fervor, confirming that the Merkel cells were necessary to put a brake on the itchy sensations. They also boosted the activity of Merkel cells that had been genetically engineered to fire when exposed to a chemical called clozapine N-oxide, and found that it reduced scratching in mice with an itchy skin condition. The finding suggests that increasing Merkel cell activity could help treat alloknesis in people, the team writes.
Past studies have shown that Merkel cells in the skin are reduced in elderly people and people with dry skin conditions. Hu and colleagues are now analyzing skin biopsies from human patients with touch-related itch problems to determine whether their Merkel cells are also depleted. The study “nicely explains why people with dry skin conditions or [the elderly] tend to have elevated itch sensitivity,” says Xinzhong Dong, a neuroscientist at Johns Hopkins University in Baltimore, Maryland, who was not involved in the study.
Still unresolved, however, is the question of where the mechanical itch signals come from in the first place, notes Mark Hoon, a neuroscientist at the National Institute of Dental and Craniofacial Research in Bethesda, Maryland. Although the evidence suggests Merkel cells help tamp down mechanical itch, the mechanism for producing the signals is still not clear, he says. “One is left wondering how it all fits together.”