A molecular window on itch

Researchers discover chemical puppet master behind the need to scratch

Long a mystery, the sensation of itch has yielded a clue. The neurons that detect itch rely on a newly identified chemical to send the “I need to scratch!” message to the brain, according to a study in mice. Remove the molecule, and the mice don’t itch, researchers report in the May 24 Science.

For people, an itch can be annoying or it can be debilitating. But researchers don’t know yet how the brain senses an itch. Treatments for itch often don’t work.

The new study takes a big step forward, says Glenn Giesler Jr., a neuroscientist at the University of Minnesota, Twin Cities. “Now we’re beginning to understand the mechanisms, and that’s got to lead to better treatments.”

Scientists believe that detection of itch starts in neurons with fibers that extend to the skin. Using chemical messengers called neurotransmitters, these cells relay their signal to other neurons in a region of the spinal cord called the dorsal horn. Once there, the signal passes from neuron to neuron until it reaches the brain.

To find out how this signaling starts, Mark Hoon and Santosh Mishra of the National Institute of Dental and Craniofacial Research in Bethesda, Md., measured which chemicals the neurons with fibers in the skin produced the most. One of the chemicals that topped the list was a neurotransmitter called Nppb, for natriuretic polypeptide b.

They engineered mice that lack the gene to make Nppb and injected itch-inducing substances under the animals’ skin. The animals barely scratched; they must have needed Nppb in the process that sends itch signals to the brain, the researchers surmise.

Hoon and Mishra next turned to the dorsal horn, where neurons must be receiving the Nppb molecules, they figured. When the researchers blocked Nppb receptors in the dorsal horn or used toxins to remove dorsal horn neurons, the mice scratched far less. In mice that still had these neurons, injecting Nppb into their dorsal horns made the animals scratch.

Because mice share many biological similarities with humans, the findings could help scientists understand how people sense itch.

Hoon notes that he and Mishra found Nppb in just a small subset of the neurons that have fibers in the skin, which could mean that only certain sensory neurons are responsible for detecting itch. Others may detect pain or temperature.

However, Hoon cautions that blocking Nppb may not be a good strategy to treat itching. Nppb could play a role in other processes in the body, so blocking the molecule from working may have side effects.

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