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Who Knew? A Neural Circuit Just for Itching

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Itch line (red) with touch, pain, and temperature lines (white) going through DRG before going to the spinal cord.

Itch-inducing agents activate a discrete population of peripheral sensory neurons that produce a signaling molecule called natriuretic polypeptide b (Nppb). The release of Nppb from these primary pruriceptive neurons triggers a dedicated itch biocircuit to generate the sensation of itch. [Images courtesy of Mark Hoon, National Institute of Dental and Craniofacial Research, NIH]

The occasional itch—be it a bug bite or rash—is annoying. But there are millions of people with chronic itching conditions, like eczema and psoriasis, who are constantly scratching their skin. This is more than a little irritation—it drastically reduces their quality of life and is a perpetual distraction. Current anti-itch treatments include topical corticosteroid creams, oral antihistamines, and various lotions. But researchers at NIH have gone beyond the skin’s surface and discovered a critical molecule at the root of that itchy feeling [1].

Mouse scratching it's earUntil now, it’s been unclear how the sensation of itching was carried to the brain. Was this a separate system, or did it use the same nerve pathways as pain, touch, or temperature? To find out, the researchers focused on a special group of nerve cells called “TRPV1 neurons,” which extend to the skin and detect temperature, various types of pain, and itch. These neurons use several chemicals to transmit signals; one of those is a neurotransmitter called Nppb. When the researchers created mice lacking Nppb, the mice became immune to itching. Even when the researchers exposed the mice to several itchy substances, such as histamine, the mice refused to scratch!

When the researchers actually removed specific spinal cord nerves that receive the Nppb itch signals, other sensations—like pain, touch, and temperature—remained intact. So we now know that in mice, and possibly in humans, there are specific nerve cells and brain circuitry that are entirely devoted to that itchy feeling. That means blocking Nppb could turn out to be a safe and effective strategy to cure itching, especially in chronic cases.

Reference: 

[1] The cells and circuitry for itch responses in mice. Mishra SK, Hoon MA. Science. 2013 May 24;340(6135):968-71.

NIH support: National Institute of Dental and Craniofacial Research