Mechanism of itching

Itching-a sensation that almost everyone has experienced.
Academically, it is described as an uncomfortable sensation transmitted by peripheral sensory neurons that can trigger the desire to scratch.

More and more evidence shows that inflammatory mediators are released into the skin's immune cells and other cell types, activating those specific peripheral sensory neurons, causing itching.

Itching can be divided into acute and chronic.

Scientists believe that acute itching is a protective response that may help us remove things that irritate the skin; chronic itching does not have this protective effect, and it may be pathological, such as atopic dermatitis (also known as atopic dermatitis).
Eczema), allergic contact dermatitis, etc.
, are all examples of chronic itching.

Chronic pruritus can have a serious impact on people's quality of life.
Taking atopic dermatitis as an example, pruritus can aggravate the symptoms of the disease.

In the United States, about 9.
6 million children and 16.
5 million adults suffer from atopic dermatitis.

However, although scientists have learned a lot about the itch that triggers the desire to scratch, there are still many mysteries about chronic itch.

We do not know what mechanism activates neurons to cause these chronic itching, and there is an urgent need for more effective treatments for chronic itching symptoms.

Now, a study published in the Proceedings of the National Academy of Sciences has revealed a molecular pathway that provides new clues to the underlying mechanisms of acute and chronic itch.

K.
Frank Austen, a professor of respiratory and inflammatory diseases, is one of the corresponding authors of the new study.
His team focuses on the molecular components that cause allergic inflammation.

Decades ago, Austen began studying a molecular pathway called Cysteine ​​Leukotriene Receptor 2 (CysLT2R).

Immunologist Isaac Chiu is the other corresponding author of this study.
He focuses on studying how the nervous system and the immune system interact.

In order to analyze the molecular mechanisms that may cause chronic itch, to understand the cause of itch and the relationship between itch and neurons, experts in two different fields decided to collaborate and conducted a series of studies in mice.

In the experimental design, they looked for gene activity related to itching in the dorsal root ganglion (DRG) neurons of mice.

It was found that in the dorsal root ganglia, cysteine ​​leukotriene receptor 2 has a high expression.

Then, in human dorsal root ganglion neurons, researchers also found high expression of cysteine ​​leukotriene receptor 2.

This led them to focus their analysis on analyzing the role of this receptor in the transmission of itching signals.

Through experiments, the researchers found that activating cysteine ​​leukotriene receptor 2 can induce itching in mice with atopic dermatitis, but the other mice in the experiment did not.

In addition, they found that mice lacking this receptor had less itch symptoms.

These phenomena all indicate that cysteine ​​leukotriene receptor 2 plays a key role in causing itching and atopic dermatitis, and may become a new target for the treatment of stubborn chronic itching.

Researchers hope that this discovery will promote improvements in the treatment of chronic itch.

Will cysteine ​​leukotriene receptor 2 become a new target for the treatment of chronic pruritus? According to the researchers, we already have montelukast, a leukotriene inhibitor targeting cysteine ​​leukotriene receptor 1 (CysLT1R), which can be used to treat asthma, but it cannot relieve itching.
), but there is still a lack of cysteine ​​leukotriene receptor 2 inhibitors that have been clinically approved.

Although targeting these receptors may be an effective way to treat inflammatory pruritus, it is still an unknown question whether the new target can be used to treat patients before an inhibitor is developed and tested in humans.
.

Austen has been studying leukotrienes since the 1970s.
This type of lipid molecules derived from white blood cells are closely related to allergies and inflammation. Regarding the results of this collaboration, he said that the immune system is much more complicated than we thought.
Understanding the involvement of nerves is a big step forward, which is also a missing part of inflammation research.

Therefore, linking neuroscience with inflammation and other fields is critical to understanding issues such as the molecular mechanisms that cause chronic itch.

# Creation team: compilation:# Reference source: https://news.
harvard.
edu/gazette/story/2021/04/study-offers-new-clues-about-what-causes-persistent-itch/ https: //www.
pnas.
org/content/118/13/e2022087118# Image source: Cover image: Kristina Nor / Pexels