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Scientists Identify Neurons That Register Itch

What is an itch? Scientists have speculated that it is a mild manifestation of pain or perhaps a malfunction of overly sensitive nerve endings stuck in a feedback loop. They have even wondered whether itching is mostly psychological (just think about bed bugs for a minute). Now a study rules out these possibilities by succeeding where past attempts have failed: a group of neuroscientists have finally isolated a unique type of nerve cell that makes us itch and only itch.

In previous research, neuroscientists Liang Han and Xinzhong Dong of Johns Hopkins University and their colleagues determined that some sensory neurons with nerve endings in the skin have a unique protein receptor on them called MrgprA3. They observed under a microscope that chemicals known to create itching caused these neurons to generate electrical signals but that painful stimuli such as hot water or capsaicin, the potent substance in hot peppers, did not.

In the new study published in Nature Neuroscience, the researchers used genetic engineering to selectively kill the entire population of MrgprA3 neurons in mice while leaving all the other sensory neurons intact. These mice no longer scratched themselves when exposed to itchy substances or allergens, but they showed no changes at all in responding to touch or pain-producing stimulation.


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The mice's behavior confirms that MrgprA3-containing neurons are essential for itch, but it does not rule out the possibility that these cells might respond to other sensations as well. To find out, the neuroscientists engineered a receptor that responds to capsaicin injected into the MrgprA3 neurons, in a type of mouse that lacks the capsaicin receptor in all its other cells. Now the only neurons that would be stimulated by capsaicin were the MrgprA3 neurons. If these cells are indeed itch-specific, injecting capsaicin into a tiny spot on the mouse's skin should make the rodent scratch instead of wincing in pain—which is exactly what happened.

“Our current study has shown experimentally for the first time the existence of itch-specific nerves,” Dong says. The discovery that itching is distinct from pain, touch or temperature sense should allow for the development of new drugs that block Mrgpr-A3 receptors, which will silence the raging itch of poison ivy or eczema without affecting any other senses.


ITCH FACTS

1660: The year the meaning of itch was first defined. Samuel Hafenreffer, a German physician, called it an unpleasant sensation that compels people to scratch.

Social itching

64: Percentage of people who scratched when watching others do so, according to a recent study.

Excessive itchiness is a symptom of:

  • Obsessive-compulsive disorder

  • Depression

  • Eating disorders

  • Delusional thinking

R. Douglas Fields an adjunct professor in the University of Maryland, College Park’s Neuroscience and Cognitive Science Program. He is author of Electric Brain: How the New Science of Brainwaves Reads Minds, Tells Us How We Learn, and Helps Us Change for the Better (BenBella Books, 2020).

More by R. Douglas Fields
SA Mind Vol 24 Issue 2This article was originally published with the title “Cell That Makes You …” in SA Mind Vol. 24 No. 2 (), p. 20
doi:10.1038/scientificamericanmind0513-20