By Kelsey Calhoun
Chronic pain gets a fair amount of attention from researchers, but chronic itch, such as eczema or psoriasis, can cause just as much distress. Chronic itch can result from a variety of skin, nervous system or systemic disorders, and many drugs, including some antidepressants, can cause terrible itch as a side effect. There are few effective treatments for such intense and chronic itching, despite being a relatively common affliction: Eczema alone affects nearly 10 percent of people worldwide.
But good news may be on the horizon. A team of scientists, including faculty and students in the MBL Neurobiology Course, have identified a new gene that promotes itching, suggesting a way forward to a better understanding and, perhaps, to powerful new therapies.
To identify genes that mediate itch, the team, led by Diana Bautista of the University of California, Berkeley, and Rachel Brem at the Buck Institute for Research on Aging, studied itch behavior across genetically distinct mouse strains. Just as eczema and allergic itch can run in families, they found that some mouse strains were more likely to develop chronic itch and could pass this trait onto their progeny. They then compared gene expression levels in the itch-prone and itch-resistant mice, specifically in the sensory neurons that innervate the skin and mediate itch sensations.
They discovered that mice naturally expressing high levels of a particular gene, HTR7, were exceptionally itchy. This caught their attention, because HTR7 codes for a serotonin receptor, and “high levels of serotonin in the skin have long been known to correlate with itch severity in a variety of human chronic itch disorders,” Bautista says. They also discovered, in a mouse model of eczema, that activation of HTR7 triggered itch-evoked scratching while ablation of HTR7 significantly diminished itch.
Some of the key work on the paper was done by three students in the MBL Neurobiology Course in 2014. Anne Olsen, Michael Kienzler, and Kyle Lyman worked with Bautista, a faculty member in the course, to identify some of the mechanisms by which activation of HTR7 promotes chronic itch signaling in the nervous system. All three students appear as co-authors on the paper.
Understanding the molecular mechanisms underlying chronic itch is of significant clinical interest and there is much more to learn. “Abnormal behavior of three cell types mediate chronic itch,” says Bautista, “skin cells, neurons, and immune system cells. We want to discover the mechanisms that promote itch, and also what long-term changes in these cell types maintain chronic conditions.” In the meantime, the HTR7 receptor offers an exciting potential drug target for new medications seeking to sooth intense itchiness.
Citation: Morita T et al (2015). HTR7 Mediates Serotonergic Acute and Chronic Itch. Neuron, DOI: 10.1016/j.neuron.2015.05.044