Researchers at the Buck Institute for Age Research in Novato and the University of California at Berkeley have discovered a genetic link that might lead to new treatments for chronic itch.
The researchers published the results of their new study this week in the online edition of Neuron.
“On the face of it you might not think chronic itch is a compelling health problem, but the clinical studies show it can be as debilitating as chronic pain. It can really drive you nuts,” said Buck associate professor Rachel Brem, one of scientists leading the study.
“Chronic itch tends to be more prevalent and debilitating in elderly people,” Brem said, hence the Buck Institute’s interest in the disorder. Eczema, the most common cause of chronic itch, affects up to 10 percent of the worldwide population.
The new research demonstrates a connection between eczema and the HTR7 gene, which is a serotonin receptor. Serotonin is a neurotransmitter created by the human body that many scientists believe is responsible for maintaining balanced moods.
The study also found that mice injected with Zoloft, an antidepressant that increases serotonin levels, scratched themselves more intensely.
“It’s a very pretty piece of work,” said Dr. Ethan Lerner, an associate professor of dermatology at Massachusetts General Hospital.
Lerner said that effective treatment for most types of chronic itch simply doesn’t exist.
“Most people prescribe antihistamines, but they don’t work very well at all,” Lerner said. “A histamine always causes hives and most people with chronic itch, or even acute itch, don’t have hives so you wouldn’t expect antihistamines to work.”
“The discovery of the gene that mediates itch came out of a survey of a bunch of genetically distinct mice,” said Brem, a geneticist who studies how and why traits differ among individuals.
The researchers administered the same itch-inducing compound to a number of strains of mice. Each of the strains was genetically different from the other. They found that the mice that itched the most all had the HTR7 gene.
The researchers later injected mice with Zoloft to gauge the result.
“Some patients who take antidepressants report itch and some don’t,” Brem said, “so we hypothesized that this side-effect of antidepressant use that has been reported in humans could be mimicked in mice. And that turned out to be true. It turned out they itched.”
The researchers also gave the itch-inducing compound to two strains of mice that were genetically identical except for the presence of the HTR7 gene. The strain without the gene displayed far less itching.
“We are really excited about these results,” said UC Berkeley neuroscientist Diana Bautista, another lead scientist on the study. “The dramatic decrease in itching suggests that HTR7 may represent a new drug target for chronic itch.”
Brem said that, in addition to eczema, altered serotonin signaling in the skin has been reported in other forms of itch, such as psoriasis and allergic itch. That suggests that the HTR7 gene might be the key for treating many different itch disorders.
Brem said treatments would not aim at reducing an individual’s overall serotonin levels, since that could have far-reaching and unpredictable results. She said instead perhaps a compound that would reduce serotonin levels could be administered topically.
Brem said the next step in her research will be the study of itch in aging mice. It is already known that some strains of mice develop dermatitis for no apparent reason as they grow old.
“This is a real age-associated disease in mice,” Brem said.