Cause of uncontrollable chronic itching uncovered
If you have ever suffered through sleepless nights due to uncontrollable itching, you know how excruciating it can be, and that not all itching is the same. Chronic itching, which can occur in medical conditions ranging from eczema and psoriasis to kidney failure and liver disease, is very different from the temporary urge to scratch after a mosquito bite - and now researchers say they have uncovered the reasons why.
In addition to nerve cells (neurons), which transmit itch signals, American and Chinese researchers say that chronic itching also employs pain neurons that intensify the itchy sensation. In other words, chronic itching appears to include more than just the nerve cells, or neurons, that usually transmit itch signals. In chronic itching, neurons that send itch signals also incorporate pain neurons to intensify the urge to itch.
In a study, published in The Journal of Clinical Investigation, the researchers created genetically modified mice that had a continuously active protein called BRAF transmitting signals inside itch neurons. Both the BRAF gene and the protein play a role in how the body responds to pain, although it remains unclear as to whether the BRAF gene plays a role in the response to itch.
After the researchers created the genetically modified mice, they were shocked to discover that they had developed a chronic itch mouse model, with the BRAF protein having the ability to switch many itch genes on and off.
"We thought the animals might be prone to feeling pain rather than itching," said Dr. Zhou-Feng Chen, director of Washington University's Center for the Study of Itch. "To our great surprise, the mice scratched spontaneously. At first, we didn't know why they were scratching, but it turns out we developed a mouse model of chronic itch."
These findings demonstrated that when the mice experienced chronic itch triggered by dry skin from an allergic rash, the itch genes similarly changed as a result of the BRAF protein control, which the researchers say may explain why chronic itching can be so incessant in comparison to the fleeting itch from a bug bite or some other skin condition.
“In normal itching, there's a fixed pathway that transmits the itch signal,” explained Dr. Chen. “But with chronic itching, many neurons can be turned into itch neurons, including those that typically transmit pain signals. That helps explain why chronic itching can be so excruciating.”
By the same token, the researchers pointed out that the genetically modified mice expressed a normal response to pain, an indication that there are significant differences in the pain and itch pathways. As a result of these findings, the possibility exists for developing new treatments for chronic itch by targeting proteins that are present in the BRAF pathway.
According to Dr. Chen, one such possibility that could be explored is through using drugs that are able to treat pain, especially given that there are certain drugs in existence that inhibit some of the same targets in patients suffering from chronic pain; thus, these could also be used to provide relief for itching.
However, Chen said that the findings of this study offer many more options for potential chronic itch treatments.
“In people, chronic itching can last for weeks, months, or even years. These mice are helping us to understand the pathways that can be involved in transmitting itch signals and the many contributors to chronic itching," said Chen.
“There are many pathways leading from BRAF, and all of these could be potential targets for anti-itch therapies.”
SOURCES: Chronic itch development in sensory neurons requires BRAF signaling pathways, Zhong-Qiu Zhao, Fu-Quan Huo, Joseph Jeffry, Lori Hampton, Shadmehr Demehri, Seungil Kim, Xian-Yu Liu, Devin M. Barry, Li Wan, Zhong-Chun Liu, Hui Li, Ahu Turkoz, Kaijie Ma, Lynn A. Cornelius, Raphael Kopan, James F. Battey, Jr., Jian Zhong, Zhou-Feng Chen, published in the Journal of Clinical Investigation, October 8, 2013.