Itch Leaves Neuroscientists Scratching Their Heads

by Aalok Mehta

December 11, 2008

For most people, an itch is nothing more than a temporary inconvenience. For others, however, it’s a source of persistent, sometimes crippling irritation for which there is no good treatment.

Now new research, announced in Washington, D.C., in November at the annual meeting of the Society for Neuroscience, is providing basic insights into what causes the distinct varieties of itch, how those sensations are transmitted to the brain and how itch and pain differ, bringing the possibility of true relief one step closer.

Far from a frivolous medical problem, itch—known medically as pruritus—“is the most common symptom seen by dermatologists,” said Ethan Lerner of Harvard Medical School. Some skin diseases, such as hives, cause itching through a histamine reaction and therefore can be treated well with antihistamines, he added.

However, treatments are lacking for the severe, persistent itching that often results from chronic conditions such as cancer, HIV and kidney disease, each of which responds poorly to existing medications.

One common model for studying such nonhistamine types of itch, Lerner said, is the tropical plant cowitch, or cowhage, which has long been used as the primary ingredient in many an itching powder. Cowitch causes a distinctly different type of itch than histamine and, earlier this year, Lerner and his colleagues reported that they had found cowhage’s active ingredient: an enzyme known as mucunain, housed at the tip of the plant’s seed pod hairs.

The new research illuminates additional differences between cowhage- and histamine-induced itch, including distinct neurological mechanisms. For example, researchers know that histamine induces itching primarily by activating fibers unresponsive to touch. On the other hand, Matthias Ringkamp, a neurosurgeon at Johns Hopkins University, and his colleagues found that cowhage exclusively activates “mechanosensitive” nerve fibers in the skin that also react to touch and heat. This difference may explain why the skin around a cowhage injection tends to become highly touch-sensitive, and it offers a useful target for new medications, Ringkamp said.

Another study suggests that the right place to treat itch may not be the skin but the central nervous system. Uncontrollable itching is one common and puzzling side effect of strong pain drugs such as morphine; Zhou-Feng Chen of Washington University in St. Louis and his colleagues found that blocking the activity of or eliminating an itch-related gene expressed in the spinal cord—the gene for the gastrin-releasing peptide receptor (GRPR)—relieves the itching without canceling out the pain relief, at least in mice.

Because GRPR can convey nonhistamine signals for itch, it may offer a general target for anti-itching medications, Chen said. But the research also reveals shatters some common ideas about itch.

“Itch has long been considered a minor form or submodality of pain, but it’s not,” Chen said. “They are two very different sensations, and in this case they can be separated.” Pain and itch are in fact opposites in some ways, since the pain of scratching can relieve itch, he said.

The assembled scientists caution that they’ve only scratched the surface on the concept of itch. “Itch is something that happens in your brain,” said Clemens Forster of the University of Erlangen-Nurnberg in Germany, who presented findings showing that histamine- and cowhage-type itch activate separate nerve pathways and that scratching seems more effective on histamine-caused itches. “But what exactly happens in the brain, we do not know yet.”