A significant amount of CysLT2 receptors, present in certain neurons, would be linked to chronic incurable itching. This discovery could open up new therapeutic avenues.
- Receptors present only on neurons linked to itching would be at the origin of this disorder when it is chronic
- Knowledge of this mechanism could pave the way for new treatments
Itching – also called skin pruritus – can be defined as a unpleasant sensation that leads to need to scratch. They can be a symptom that accompanies a dermatological disease, such as eczema. This pathology, also called atopic dermatitis, affects genetically predisposed people. This severe itching is uncomfortable, chronic, sometimes incurable and can decrease the quality of life of patients. Researchers have just identified one of the mechanisms that could explain this skin pruritus. Their work has been published in the review Proceedings of the National Academy of Sciences (PNAS). According to them, the quantity of CysLT2 receptors would be involved. A receptor is a structure present on the membrane or inside a cell. Its role is to receive messages that will modulate cellular activity.
The itching goes up to the brain
“Itching originates from a subset of neurons, and acute itchiness may be a protective response to help us eliminate something that is irritating the skin, believes Chiu, co-author of the study. However, chronic itching is not protective and can be pathological. The underlying mechanism that activates neurons and causes chronic itching is not well understood and new treatment is needed.“Indeed, itching is born in the nerve endings present on the surface of the skin, at the level of specific receptors. This information is then transmitted to the sensory ganglia, to the spinal cord and ends up going up the nerve path to the brain. Thus, it activates sensory, emotional and motor brain areas.
Presence of CysLT2R receptors could be the cause of itching
The researchers therefore wanted to determine the mechanisms that trigger this need to scratch in the context of chronic itching. To arrive at their results, they analyzed the activity of the sensory ganglia of the dorsal root – linked to itching in mice – which contain neurons. Thus, they observed a significant amount of CysLT2 receptors only present on itch-related neurons. After further experiments and research, they concluded that the activation of these receptors induced a skin pruritus in some mice with eczema, but not all. Indeed, mice that lacked CysLT2R receptors suffered less from itching. The presence of CysLT2R receptors could therefore be the cause of the itching and, possibly, the development of eczema.
Towards new therapeutic avenues?
“The last ten years of research in the field of chronic itching have shown the importance and the complexity of the interactions between the immune system and the nervous system, points out Tiphaine Voisin, lead author of the study. It was very exciting to explore the contribution of leukotrienes.“The researchers continued their research by studying leukotrienes. These are inflammation mediators, particularly bronchial in the context of asthma. To treat this pathology, one of the solutions proposed is inhibition (c (i.e. slowing down or stopping) leukotrienes, by targeting the CysLT1R receptor. This has no effect on itching since it would be necessary to be able to target CysLT2R. However, currently, no inhibitor has been validated scientifically to do so. The authors of the study therefore hope that future research will make it possible to find this inhibitor which could, in the long term, offer new therapeutic avenues. Thus, once the nervous system is treated, the body’s immune response would work better and reduce the itching.”The immune system is much more complex than we thinksays Frank Austen. Understanding the involvement of nerves is a huge step forward. This was a missing element in the study of inflammation. In my opinion, it is extremely important to connect neuroscience with those who study inflammation. ”
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