New research is looking into how our bodies sense and transmit itchiness to the brain.
Light touches play an important role in our daily lives. Between cuddling, picking up fragile objects, and performing tasks that require precision, we use the sensation to guide many of our activities. It’s also an essential part of the body’s defense system, telling us, among others, if we’re covered in biting insects such as ticks or mosquitoes — via that oh-so-pleasant sensation of itchiness.
“The takeaway is that this mechanical itch sensation is distinct from other forms of touch and it has this specialized pathway within the spinal cord,” says Salk Institute Professor Martyn Goulding, senior author of the new study.
The team looked at how neurons in the spinal cord carry these itchy signals to the brain. They hope that the findings will help lead to new drugs to treat chronic itch, which occurs in such conditions as eczema, diabetes, and even some types of cancer.
Goulding and his colleagues had previously found a set of inhibitory neurons in the spinal cord that keep the itchiness pathway locked down most of the time. Inhibitory neurons act as brakes on neural circuits, dampening their activity. Without these neurons — which produce the neurotransmitter neuropeptide Y (NPY) — the pathway is constantly active, causing chronic itching.
What the team wanted to find out know was how the signal encoding this sensation is transmitted to the brain, making us feel the itch. One of the team’s hypotheses was that when NPY inhibitory neurons are missing, the nerve bundles in the spinal cord that transmit light touch get stuck on the “on” setting — which creates a self-amplifying loop. The team identified a population of such (excitatory) neurons in the spinal cord that express the receptor for NPY, the so-called Y1 spinal neurons
To test if these were indeed behind the self-amplifying loop of itchiness, the team selectively removed the NPY “brake” and Y1 “accelerator” neurons in mice to see the effects.
Without Y1 neurons, they report, the mice didn’t scratch, not even in response to light-touch stimuli that normally make them scratch. When the team gave them drugs to activate the Y1 neurons, the mice scratched spontaneously even in the absence of any touch stimuli. The team was then able to link NPY neurotransmitter levels to Y1 neuron excitability — showing that NPY controls our sensitivity to light touch. The findings are also supported by other research which found that people with psoriasis have lower than average levels of NPY.
While the study shows how itchy signals go through the spinal cord, more research is needed to understand the full pathway. There are other neurons that likely mediate its transmission and final response in the brain, the team explains.
“By working out mechanisms by which mechanical itch is signaled under normal circumstances, we might then be able to address what happens in chronic itch,” says David Acton, a postdoctoral fellow in the Goulding lab and the study’s first author.
The paper “Spinal Neuropeptide Y1 Receptor-Expressing Neurons Form an Essential Excitatory Pathway for Mechanical Itch” has been published in the journal Cell Reports.