American poet Ogden Nash once wrote, “Happiness is having a scratch for every itch.” Science has come a long way toward understanding what causes the itching sensation, and now an Israeli-American joint research team could solve Nash’s happiness problem and put an end to a lot of itchiness.

Some of the stimulus that causes itching, including the itch caused by mosquito bites or exposure to allergenic materials, is caused by the mechanism that causes the immune system to respond. In response histamine is released, which triggers the inflammatory response and leads to the feeling of itchiness in the skin.

There are other common factors that cause the itch sensation which operate under different pathways and reflect a number of medical disorders. Among these are itchiness as a result of dry skin, eczema or atopic dermatitis, also known as skin asthma, which mainly affects babies and children.

The new research reveals the existence of neurons that detect histamine and non-histamine itch-provoking ligands in response to various stimuli.

The first stage was to determine whether the various stimuli that provoke the itch work through similar physiological mechanisms.

The scientists used a method employed to turn off pain neurons and used lidocaine, an anesthetic that penetrates the cells and blocks the sodium channels that are responsible for the sensations. The scientists gave the lidocaine an electric charge to prevent it from penetrating the cells and anesthetizing them as well.

In experiments done on mice and rats the researchers proved that the charged lidocaine did not penetrate the cells but did infiltrate the neurons that were open in response to the painful stimulation, leading to the silencing of the feeling of pain in these neurons.

The mice were exposed to capsaicin, the active ingredient in chili peppers, and in response the pain neurons opened up. The scientists discovered that not only the pain sensation but also the itch caused by the histamine release responded to the electrically-charged lidocaine.

Dr. Alexander Binshtok of the Hebrew University in Jerusalem was one of the lead researchers of the joint team from Hebrew University and Harvard University. Binshtok, of the Department of Medical Neurobiology of the Faculty of Medicine and the Edmond and Lily Safra Center for Brain Sciences, explained that the material penetrated the neurons at the level of the skin, where the sensation of the itch is created in response to the histamine. That silences the neurons that transmit information to the brain via the spinal cord, stopping the itching sensation.

In the next phase of the experiment a different material was injected that did not cause the release of histamine but worked through a different mechanism to cause the itching. The itch mechanism without the histamine worked differently, said Binshtok, but the charged lidocaine still worked.

The research was published two weeks ago in the journal Nature Neuroscience, in an article titled, “Activity-dependent silencing reveals functionally distinct itch-generating sensory neurons.”

The research was supported by the U.S. National Institutes of Health. Other Hebrew University scientists on the team included Sagi Gudes and Felix Blasl. Participants from Harvard included Prof. Clifford Woolf, Jared Sprague and David Roberson.

The scientists are expanding their research to include larger animals, with the eventual goal of carrying out human clinical trials.

Earlier studies have already shown that the parts of the nervous system involved in itching are similar in rats and humans. The researchers hope to find ways to apply the lidocaine using a topical cream rather than by injection, to help prevent itching due to various causes.

Open gallery view A mosquito. Credit: Bloomberg