We've Found the Molecule That Causes ItchinessS

Researchers have discovered the molecular link between the cells in skin that sense itching and the nerve cells that relay the perception of that itch to the brain. Take that molecule away, and the itchy sensation vanishes. So far, the molecules, cells and circuitry in question have been identified in mice, but this discovery stands to improve research into itch-prevention in humans, as well.

The research, published in the latest issue of Science, shows that a small neurotransmitter called natriuretic polypeptide b (Nppb) is required to initiate the sensation of feeling itchy – due to an allergic reaction, an infection, or a dermatological disorder like eczema. A team led by National Institutes of Health researcher Mark Hoon discovered that mice which were genetically engineered to not produce the molecule were impervious to a broad range of itch-inducing chemicals and stimuli.

"We tested Nppb for its possible role in various sensations without success," said Santosh Mishra, first author on the study, in a statement. "When we exposed the Nppb-deficient mice to several itch-inducing substances, it was amazing to watch. Nothing happened. The mice wouldn't scratch."

In later investigations, the researchers injected Nppb into the animals and found it to induce scratching, further suggesting that the neurotransmitter serves as a universal first step in the itch-response pathway. Moreover, when Mishra, Hoon and their colleagues removed the cells in the mice's spinal cords that Nppb acts upon – a receptor neuron named Npra – they found the mice "displayed normal responses to thermal, touch, and painful stimulation," but they exhibited "a dramatic reduction in scratching evoked by histamine."

In other words: the removal of these cells led to a decrease in itch sensitivity, but not in other somatosensory responses. This, write the researchers, suggests that Nppb acting on Npra neurons are the initial steps in a dedicated biocircuit that communicates the sensation of itchiness to the brain.

Ultimately, the researchers conclude that Nppb "is both necessary and sufficient for transmission of peripheral signals that induce stereotypic itch responses." And yet, Nppb is an important molecule to processes — unrelated to itch response — in the heart, kidneys and elsewhere, which will make it tricky to target specifically in treatments geared toward itch control without triggering undesirable side effects. That said, being familiar with the neurotransmitters, cells, and neural circuitry specific to itch response at such unprecedented levels of detail should enable researchers to pursue newer, more focused avenues of research into itch-prevention.

"Now the challenge is to find similar biocircuitry in people, evaluate what's there, and identify unique molecules that can be targeted to turn off chronic itch without causing unwanted side effects," said Hoon. "So, this is a start, not a finish."

The researchers' findings are published in the latest issue of Science.

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