Two distinct brain pathways responsible for itch have been identified in mice. Future therapies targeting these neural circuits could improve treatments for chronic skin conditions such as psoriasis and eczema.
Two types of stimuli trigger itching: mechanical, such as hair tickling your neck, or chemical, such as an allergic reaction. Previously, at the Salk Institute for Biological Sciences in San Diego, California, and his colleagues had identified the brain mechanism underlying chemical itch, but it was unclear if the same circuitry governed mechanical itch, too.
To find out, they stroked eight mice with a thin hair 10 times and measured how often the animals scratched themselves in response. Half of the mice had had neurons in the parabrachial nucleus (PBN) 鈥� a brain region involved in relaying sensory information 鈥� silenced using chemogenetics, a technique to activate or deactivate cells with drugs. All the mice were genetically engineered to be more sensitive to mechanical stimulation to make sure they would reliably scratch in response.
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Mice with silenced PBN neurons scratched themselves about 66 per cent less of the time than mice in the control group, indicating mechanical itch is regulated by the PBN.
In a separate group of mice, the researchers induced mechanical itch in four of the animals and chemical itch in another five. After euthanising the mice, the team bathed slices of their brains in a solution that binds to a protein associated with recent neuron activity, making it glow under a microscope. The researchers found that all the mice in the mechanical itch group had activation in the same types of neurons, and that these neurons were different from those activated by chemical itch, indicating the two types of itch are governed by distinct neural pathways.
To understand the relationship between these pathways and chronic itch 鈥� persistent, spontaneous scratching 鈥� the researchers used a toxin to kill neurons in each circuit in different groups of mice with eczema-like symptoms. They found both pathways cooperate to drive chronic itch in the animals. 鈥淚f we can understand what these neural pathways look like, we place ourselves in a position where we can become a little cleverer in terms of how to ameliorate or disrupt these,鈥� says Goulding.
For instance, future drugs targeting these pathways could help treat chronic itching associated with skin conditions such as psoriasis and eczema.
Neuron
