A hand scratching at a pruritus on arm April 2010 (Orrling and Tomer S.)
Researchers from the Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research (NIDCR), Bethesda, U.S., found a protein that translates the sensation of itch from the skin to the brains of mice. The findings, published in the journal Science, put in order several pieces in our understanding of itching and reveal a new target for clinical treatment.
Itching has been characterized as a physiological self-protective alarm mechanism activated by our body to prevent external agents from doing harm to our skin. It is also the first symptom in several conditions, such as eczema. We itch and scratch in order to remove irritants but itching can affect the quality of life, especially of some people with chronic itch. No cure has been found yet and the main reason is because scientists do not know the molecular reactions triggered by itching that take place in our neurons.
Few years ago, researchers have found that itching includes their own lot of nerves and pathways in the body, distinct of e.g. pain networks. Particularly, researchers have shown that distinct receptors on the membrane of neurons, e.g. gastrin-releasing peptide receptor (GRPR), and the transient receptor potential cation channel subfamily V member 1 (TRPV1), dedicated membrane proteins involved in the transport of molecules, are translating the initial signals from the skin into the feeling of itching in the brain. But the picture of itching networks was quite incomplete, and scientists could not explain what triggers itching.
Neuroscientists Santosh Mishra and Mark Hoon looked for new molecules that are involved in the itching sensation. To do that, they looked for differences in neurons between normal mice and mice which had the TRPV1 gene deleted. They found a protein, natriuretic polypeptide (Nppb), expressed only in a subset of neurons, but not in the neurons of mice with TRPV1 deleted. The Nppb-expressing neurons were mainly the primary sensory neurons, placing Nppb at the top of the pathway triggering the sense of itching.
To study further its function, the researchers generated mutant mice with the Nppb protein deleted. They found that the mice without Nppb (Nppb-/-) had no urge to scratch an itch mediated by the scientists. Other senses, such as pain or temperature were unaffected. What was remarkable was that the Nppb-/- mice did not respond to any pluritogen (compounds that cause itching). This means that Nppb is a protein important for all kinds of itches, contrary to other proteins which were necessary for a small subset of pluritogens.
“Our work shows that itch, once thought to be a low-level form of pain, is a distinct sensation that is uniquely hardwired into the nervous system with the biochemical equivalent of its own dedicated landline to the brain,” said Dr Hoon, who led the study.
Itching can arise from dry skin, insect bites, psoriasis, allergies or many other reasons. Me, while writing this article, i am scratching my leg due to dry skin. You, while reading this article, you might be scratching your own arm or maybe your nose. But we all have the same reactions in our body: distinct neurons on our skin, the dorsal root ganglia (DRG) neurons, activate Nppb, which in turn activates its receptor, Npra, which will then activate gastrin-releasing peptide (GRP) and GRP receptors of the spinal cord and eventually transmit the signal to the brain. The last molecular steps after GRP activation remain to be identified.
And why does scratching brings the feeling of relief, even temporarily? In 2007, scientist found that scratching decreased the activity in certain areas of the brain which are associated with memory and are activated when we remember unpleasant sensations or difficult experiences. “It seems that the reflex of scratching suppresses the emotional components of the itch, the misery of it, and brings about its relief,” said Dr. Yosipovitch, of Wake Forest University Baptist Medical Center, who led the 2007 study.
What needs to be further studied is whether these reactions are the same in humans, as they are in mice. “I’d be extremely surprised if it didn’t work the same way in people,” said Dr Hoon.
