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LA JOLLA, Calif. — Have an itch that always seems to come back? Researchers from the Salk Institute are finally shedding some light on the science of scratching. Their study analyzed the brain patterns underlying itch-scratch responses and chronic itch conditions in mice, and discovered different neural pathways drive different varieties of itch.
Most people consider the occasional itch as nothing more than a mere annoyance, but it's worth remembering that on an evolutionary level itchiness serves a genuine purpose. Itching serves as a protective signal for countless animals, including humans, to prevent parasites from introducing potentially hazardous pathogens into the body.
For instance, if a mosquito lands on an individual’s arm, they will often sense its presence on their skin and quickly scratch the spot to remove it. That type of itchiness is “mechanical,” while itchiness resulting from an irritant (such as the mosquito’s saliva if it bites that person’s arm) is a “chemical” itch.
While both types of itchiness generally result in the same sensation, this latest research now indicates that, in mice, one dedicated brain pathway drives the mechanical sensation, while a separate and distinct neural pathway encodes chemical itchiness.
All in all, researchers uncovered that a small population of neurons relay mechanical itch information from the spinal cord to the brain, and identified the neuropeptide signals that regulate both itch types.
“This study provides fundamental insights into how these two forms of itch are encoded by the brain and 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 Martyn Goulding, professor and holder of the Frederick W. and Joanna J. Mitchell Chair, in a media release.
Your brain has special alarm for itches
These discoveries build on earlier work conducted in Goulding’s lab that identified the neurons in the spinal cord controlling mechanical itch, but not chemical itch. This time around, members of Goulding’s lab teamed up with co-corresponding author Sung Han, assistant professor and holder of the Pioneer Fund Developmental Chair. Prof. Han previously discovered that a small region of the brain serves as an alarm center for threat signals, both external and internal within the body.
Prof. Han's team noticed that a specific group of neurons appeared especially crucial for encoding threat signals. So, Goulding's lab opted to focus on those neurons and ascertain if they play a special role in relaying mechanical itch signals to this alarm center.
Researchers used a combination of genetic approaches and wearable miniaturized microscopes that allowed the team to actually see itch-induced activity in single neurons of mice. This led to the discovery that by removing an inhibitory pathway involved in itching, they could activate a mechanical itch. Then, after observing subsequent activity and changes occurring in the brainstem, study authors saw that different cells were responding to either mechanical or chemical itches. This helped the research team classify distinctions between a chemical itch pathway and a mechanical itch pathway, as well as clearly identify the molecules integral to regulation.
“We found that if you sensitize one pathway, you can stimulate a pathological itch state, and vice versa,” Prof. Han explains. “This indicates that these two pathways act together to drive chronic itch.”
Itching seems to get worse with age
Moving forward, the research team wants to examine where in the brain these pathways converge, and then explore the areas of the brain receiving signals that determine whether we decide to scratch an itch or not. Study authors also want a clearer understanding of how the spinal cord and brainstem differentiate between pain and itch.
“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,” Prof. Goulding concludes. “Given that chronic itch is an intractable problem, our findings should help leverage the development of new therapies for treating it.”
The study is published in the journal Neuron.
