Uncontrollable chronic itching, often a symptom of eczema and psoriasis, is completely different from the temporary, milder itching a person experiences through a mosquito bite. And now, scientists say they have uncovered the mechanisms as to why this is.
Researchers from the US and China say that as well as involving the usual suspects that transmit itch signals - "itch" nerve cells or neurons - chronic itching also utilizes pain neurons, intensifying the sensation of the itch.
To reach their findings, published in The Journal of Clinical Investigation, the researchers created genetically modified mice who have a continuously active protein, called BRAF, transmitting signals inside itch neurons.
According to the scientists, both the BRAF gene and the protein it makes play a part in the body's response to pain, but it is not clear if the gene plays a role in the response to itch.
Researchers say that chronic itching may be caused by pain neurons intensifying the itch sensation.
Following the creation of the mice, the researchers were shocked to find they had developed a chronic itch mouse model.
"We thought the animals might be prone to feeling pain rather than itching," explains 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."
Findings 'explain excruciating chronic itching'
Through further investigation of the mouse models, the researchers found that the BRAF protein has the ability to switch many itch genes on and off.
When the mice experienced chronic itch, brought on by dry skin and allergic contact dermatitis, the itch genes demonstrated similar changes of expression as a result of the BRAF protein control.
Furthermore, analysis of the mice showed that gastrin-releasing peptide (GRP) - a substance the researchers previously discovered transmitted itch signals to a gastrin-releasing peptide receptor (GRPR) gene in the spinal cord - doubled in activity.
Dr. Chen says these findings may explain why chronic itching can be so incessant, compared with standard temporary itching:
"In normal itching, there's a fixed pathway that transmits the itch signal. 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."
However, the researchers note that the genetically modified mice showed a normal response to pain, which indicates significant differences in the pain and itch pathways.
Potential for new chronic itch treatments
The scientists say that their findings mean that by targeting proteins that are present in the BRAF pathway, new methods could be explored for the treatment of chronic itch, particularly as there are currently very effective treatments available.
Dr. Chen says one possibility that could be explored is through using drugs that are able to treat pain. He notes that certain drugs are used to inhibit some of the same targets in patients suffering from chronic pain, and these could also calm the itchy sensation.
But he adds that this research offers many more options for potential chronic itch therapies:
"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.
There are many pathways leading from BRAF, and all of these could be potential targets for anti-itch therapies."
Earlier this year, Medical News Today reported on a study suggesting that itch and pain have separate circuits.