Researchers have figured out what’s behind a vicious cycle: why scratching an itch makes you itch even more.
A new study with mice finds that scratching causes the brain to release serotonin, which intensifies the itch sensation. The same is believed to occur in people.
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The findings provide new clues that may help break that cycle, particularly in people who experience chronic itching.
Scientists have known for decades that scratching creates a mild amount of pain in the skin, says senior investigator Zhou-Feng Chen, professor of anesthesiology, of psychiatry, and of developmental biology and director of the Center for the Study of Itch at Washington University in St. Louis.
That pain can interfere with itching—at least temporarily—by getting nerve cells in the spinal cord to carry pain signals to the brain instead of itch signals.
“The problem is that when the brain gets those pain signals, it responds by producing the neurotransmitter serotonin to help control that pain,” Chen says. “But as serotonin spreads from the brain into the spinal cord, we found the chemical can ‘jump the tracks,’ moving from pain-sensing neurons to nerve cells that influence itch intensity.”
Scientists uncovered serotonin’s role in controlling pain decades ago, but this is the first time the release of the chemical messenger from the brain has been linked to itch, Chen says.
Itch and pain
For the study, published in the journal Neuron, researchers bred a strain of mice that lacked the genes to make serotonin. When those genetically engineered mice were injected with a substance that normally makes the skin itch, the mice didn’t scratch as much as their normal littermates.
But when the genetically altered mice were injected with serotonin, they scratched as mice would be expected to in response to compounds designed to induce itching.
“So this fits very well with the idea that itch and pain signals are transmitted through different but related pathways,” Chen says. “Scratching can relieve itch by creating minor pain.
But when the body responds to pain signals, that response actually can make itching worse.”
Although interfering with serotonin made mice less sensitive to itch, it’s not practical to try to treat itching by trying to block the release of serotonin.
Serotonin is involved in growth, aging, bone metabolism, and in regulating mood. Antidepressants like Prozac, Zoloft, and Paxil increase serotonin levels to control depression. Blocking serotonin would have far-reaching consequences throughout the body, and people wouldn’t have a natural way to control pain.
First, you scratch
Instead, it might be possible to interfere with the communication between serotonin and nerve cells in the spinal cord that specifically transmit itch. Those cells, known as GRPR neurons, relay itch signals from the skin to the brain, Chen says. To work toward that goal, he and colleagues isolated the receptor used by serotonin to activate these neurons.
To do this, they injected mice with a substance that causes itching and also gave the mice compounds that activated various serotonin receptors on nerve cells. Ultimately, they learned that a receptor known as 5HT1A was the key to activating the itch-specific GRPR neurons in the spinal cord.
To prove they had the correct receptor, the researchers also treated mice with a compound that blocked that receptor, and those mice scratched much less.
“We always have wondered why this vicious itch-pain cycle occurs,” Chen says. “Our findings suggest that the events happen in this order. First, you scratch, and that causes a sensation of pain. Then you make more serotonin to control the pain. But serotonin does more than only inhibit pain. Our new finding shows that it also makes itch worse by activating GRPR neurons through 5HT1A receptors.”
