Everyone’s felt the relief of scratching a particularly annoying itch, but some people suffer from chronic itch conditions which can impair their quality of life and lead to permanent skin damage.
Normally, the sensation of itch is a protective signal that animals use to prevent parasites from introducing potentially hazardous pathogens into the body. There’s “mechanical” itchiness, triggered by something like a crawling insect on your skin, and “chemical” itchiness caused by an irritant like mosquito saliva.
Now, a new study in Neuron has identified the small populations of neurons that relay mechanical itch information from the spinal cord to the brain, as well as the neuropeptide signals that regulate both types of itches. The study was done in mice.
“This study provides fundamental insights into how these two forms of itch are encoded by the brain and it opens up new avenues for therapeutic interventions for patients that suffer from a range of chronic itch conditions, including ectopic dermatitis and psoriasis,” says co-corresponding author Professor Martyn Goulding, from the Molecular Neurobiology Laboratory at the Salk Institute for Biological Studies, US.
Previous research has shown that separatee neurons in the spinal cord control mechanical and chemical itch, and but the pathways that transmit this sensory information to the brain to evoke the perception of an itch was unknown.
To investigate, the team used genetic analysis alongside wearable miniaturised microscopes to allow them to see itch-induced activity in single neurons of mice.
They found that, in the spinal cord, spinoparabrachial neurons expressing the genes Calcrl and Lbx1 are essential for generating scratching responses to mechanical itch stimuli. Two separate populations of neurons, both found in a region of the brainstem called the parabrachial nucleus, are responsible for relaying mechanical and chemical itch to the brain.
In chronic itch these pathways for both mechanical and chemical itch are persistently hyperactivated.
“We found that if you sensitise one pathway, you can stimulate a pathological itch state, and vice versa. This indicates that these two pathways act together to drive chronic itch,” says co-corresponding author Sung Han, Assistant Professor in the Clayton Foundation Laboratories for Peptide Biology at Salk.
Next, they plan to investigate where these pathways converge in the brain and the parts of the brain that receive signals that determine the decision of whether to scratch an itch or not.
“The prevalence of chronic itch increases as we age. For this reason, we would also like to understand more about what is happening to the neural circuits that relay itch as we get older,” says Goulding.
“Given that chronic itch is an intractable problem, our findings should help leverage the development of new therapies.”