Getting to the bottom of itch

Scientists have identified a new molecule responsible for triggering the itch sensation. It has been previously found that itch, like pain and thermal sensation, is transmitted to the brain by certain sensory neurons that express an ion channel known as TRPV1, but the trigger for these potentials was unknown. Hoon and Mishra, at the National Institute of Dental and Craniofacial Research in the USA, have identified the activating molecule as natriuretic polypeptide b (Nppb).

The researchers created mice in which Nppb expression was knocked out and showed that the normal responses to touch, pain and thermal changes were preserved in these animals. They then injected prurigenic chemicals – ones that induce itch – under the skin and recorded the number of scratching bouts induced. In comparison to normal mice, the chemicals had no effect on the Nppd-deficient mice.

Next, they injected Nppb into the spinal cords of normal and Nppd-deficient mice and found that this triggered scratching in both types of mouse. Using in situ hybridisation, the researchers showed that Npra, the Nppb receptor, is found on neurons in the dorsal horn of the spinal cord, where the TRPV1-expressing neurons terminate. After killing these secondary neurons with a targeted toxin, they were able to show that scratching in response to injection of the prurigenic, histamine, was significantly reduced. Overall, these findings indicated that Nppb is a neurotransmitter or neuromodulator released by primary sensory afferents into the spinal cord, where it acts on further neurons that carry the signal on towards the brain.

A better understanding of the pathways responsible for itching may eventually help pave the way for novel therapies for patients who experience chronic itch; for example, due to eczema, psoriasis or even liver disease.

This research was published in the 24th May edition of Science: http://www.sciencemag.org/content/340/6135/968.long