IT’S A MADDENING cycle that has affected us all – it starts with an itch that triggers scratching, but scratching only makes the itchiness worse. 

Researchers have now revealed the brain mechanism driving this uncontrollable itch-scratching feedback loop. 

Itching can be triggered by a wide range of causes, including allergic reactions, skin conditions, irritating chemicals, parasites, diseases, pregnancy, and cancer treatments. 

The itch-scratching cycle can significantly impair quality of life and lead to serious skin and tissue damage. 

In a study published in the Neuron journal, researchers showed the activity of a small subset of neurons, located in a deep brain region called the periaqueductal gray, tracks itch-evoked scratching behaviour in mice. 

Recent studies have identified specific subtypes of neurons in the spinal itch circuit, including cells that express the gastrin-releasing peptide receptor (GRPR).

However, relatively little is known about the brain regions involved in itch processing.

Study author Yan-Gang Sun, of the Chinese Academy of Sciences, and his team suspected that the periaqueductal gray could be involved, in part due to its critical and well-known role in processing related sensory information such as pain.

“Effective treatment for chronic itch is still lacking, which is largely due to our limited knowledge about the neural mechanism of itch,” Sun said. 

“Our study provides the starting point to further decipher how itch is processed and modulated in the brain. Eventually, this might lead to the identification of new therapeutic targets.” 

Mice experiment

In the new study, the researchers first recorded from periaqueductal gray neurons in freely moving mice that were induced to scratch. This was done with either histamine or an antimalarial drug called chloroquine. 

Itch-induced scratching behaviour tracked the activity of a specific set of neurons that produce a neurotransmitter called glutamate and neuropeptide called tachykinin 1 (Tac1). 

When researchers removed the Tac-1 neurons, itch-induced scratching decreased significantly. 

In contrast, stimulation of these neurons triggered spontaneous scratching behaviour, even without histamine or chloroquine. 

Sun said that little is know about how the itch circuit evolved, despite its importance for the survival of animals. 

“Itch sensation plays a key role in detecting harmful substances, especially those that have attached to the skin,” he said. 

“As itch leads to scratching behaviour, this allows the animal to get rid of the harmful substances. In some cases, the lesions caused by scratching can evoke strong immune responses, which might help to combat the invaded substances.”