Itch is a protective mechanism in animals, helping to ward off parasites that might introduce harmful pathogens into the body. For instance, when a mosquito lands on someone’s arm, the immediate reaction to its touch is to scratch the area to dislodge it. This type of itch, triggered by physical contact like that of a crawling insect, is referred to as “mechanical” itch. It contrasts with “chemical” itch, which can be caused by irritants such as mosquito saliva upon biting. Despite leading to the same scratching response, recent research conducted by scientists at the Salk Institute has uncovered that a specific brain pathway in mice is responsible for the sensation of mechanical itch. At the same time, another path is responsible for chemical itch sensations.
The study, published in Neuron on April 5, 2023, highlights that a select group of neurons transmit mechanical itch information from the spinal cord to the brain, pinpointing the neuropeptide signals involved in managing both itch types. Martyn Goulding, a co-corresponding author of the study and holder of the Frederick W. and Joanna J. Mitchell Chair, emphasized the significance of understanding how the brain encodes these two itch forms. He noted the potential for these insights to pave the way for new treatments for chronic itch conditions, such as eczema and psoriasis.
This breakthrough builds upon Goulding’s previous research that identified the spinal cord neurons responsible for mechanical, but not chemical, itch. Collaborating with co-corresponding author Sung Han, who discovered a brain region acting as an alert centre for various threats, the team focused on neurons linked to mechanical itch communication to this centre.
With genetic techniques alongside innovative wearable microscopes, the researchers could observe itch-induced neuron activity in mice. They discovered that turning off an inhibitory itch pathway could trigger a mechanical itch response. Observations of different responses in the brainstem to mechanical and chemical itches enabled the researchers to distinguish between the two itch pathways and identify critical molecules regulating them.
Han pointed out the interplay between these pathways in perpetuating chronic itch, suggesting a combined approach might offer new treatment solutions. The research team is now looking to explore where these pathways intersect in the brain and how the brain decides whether to respond to an itch. They are also interested in distinguishing between pain and itch signals at the spinal cord and brainstem levels.
With chronic itch becoming more prevalent with age, the team aims to delve deeper into the changes in neural circuits responsible for itch transmission as we age. Goulding expressed hope that their findings could contribute to developing effective treatments for chronic itch, a currently challenging to manage.
The study also involved contributions from Xiangyu Ren, Shijia Liu, Amandine Virlogeux, Sukjae J. Kang, Jeremy Brusch, and David Acton of Salk, alongside Yuanyuan Liu from the National Institutes of Health, and Susan M. Dymecki from Harvard Medical School.
More information: Xiangyu Ren et al, Identification of an essential spinoparabrachial pathway for mechanical itch, Neuron. DOI: 10.1016/j.neuron.2023.03.013
Journal information: Neuron Provided by Salk Institute
