Group of Neurons May Be Shutoff Switch for Itch

by Elizabeth Norton Lasley

May 20, 2009

Scratching provides quick relief for an itch, but when done incessantly it can set the stage for skin damage, infection and a vicious cycle that makes the itching worse. Treatments that bring the same relief without the actual scratching would be a boon not only to those with everyday itches but to people with chronic skin problems and even systemic disorders, such as Hodgkin’s disease, AIDS and some liver and kidney diseases, which cause uncontrollable itching due to nerve damage.

A new study provides a starting point in the hunt for scratchless itch relief. Glenn Giesler and colleagues at the University of Minnesota have shown that scratching decreases the activity of certain spinal cord neurons that are stimulated by other sensations, such as itching, temperature or pain. They reported their findings online in the April 6 Nature Neuroscience.

Research since the early 1900s implicates the spinal cord as a probable shutoff site for the itch signal. Scientists have known since 1912 that patients undergoing cordotomy—the partial severing of the spinal cord to relieve otherwise untreatable pain—cannot feel itching below the lesion. More recent studies show that spinal cord neurons in a circuit running to the brain’s thalamus increase their firing rate in response to itch-producing substances such as histamine.

Giesler, project leader Steve Davidson and colleagues showed that these same neurons, called spinothalamic tract (STT) neurons, decrease their firing rate in response to scratching—but only during an itch. Working with anesthetized monkeys, the investigators used small electrodes to record the activity of individual neurons. They then injected histamine into an area of the paw that corresponds to the neurons.

The result was a burst of cell firing, reflecting the itching the animals would have felt had they been awake. But when the paw was scratched with an imitation monkey hand—complete with imitation fingernails—the neurons’ firing decreased by about 40 percent.

(The researchers had developed the artificial hand in previous studies that used the itchy spines of the cowhage plant. Because these particles filled the lab, making the researchers itchy, too, they had ample opportunity to test the artificial hand on themselves. “It works like a champ,” Giesler observes.)

To rule out the possibility that the neurons had temporarily stopped firing because they were tired from all the stimulation, the researchers applied a painful stimulus, capsaicin, to the same area of the foot. The cells’ firing rates increased even more—indicating that the neurons were perfectly capable of responding and that scratching-induced suppression of activity occurs only if the area is itchy.

“Our data support the idea that the cutoff for the itch sensation is in the spinal cord,” says Giesler. “But it’s likely that other mechanisms are still involved.”

One possibility, he says, is that an inhibitory signal is being sent from the brain through the STT neurons. Another explanation might be that the combination of itch and scratch triggers a third, “auxiliary” neuron that shuts down the itch sensation. The scientists will test both scenarios, he says.

Giesler also cautions that most types of itch are not related to histamine and may work through different mechanisms than the one highlighted in the study. “What our work provides is a place to start looking,” he says.

But although work from the Giesler lab shows that histamine and nonhistamine types of itch are signaled by separate pathways, STT neurons could still be a kind of master switch for itch, says Earl Carstens, a neurobiologist at the University of California, Davis, who studies itch but was not involved in this research

“An important implication of the finding is that all types of itch could be treated by drugs that mimic the inhibitory effect of scratching,” he says. “The work provides a good target to develop drugs for chronic itch from many causes,” a disorder that is poorly treated by antihistamines or other drugs.