Giving a good scratch to an itch is probably the most satisfying sensation one can feel, but according to a new study from Washington University School of Medicine in St. Louis, nothing is worse than scratching, since it causes the brain to release serotonin, which intensifies the itch sensation.

The research published in the journal Neuron states that the study conducted on mice provides insight into how to prevent itchy sensations in humans, especially those suffering from chronic itching. It is a well-known fact that scratching blocks the itching sensation. The pain that is accompanied by scratching manages to temporarily distract the brain from the itch. These pain signals are transmitted to the brain by nerve cells just like an itchy feeling is also transmitted by another set of nerve cells.

"The problem is that when the brain gets those pain signals, it responds by producing the neurotransmitter serotonin to help control that pain," said senior author Zhou-Feng Chen in a statement. "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."

While the role of serotonin as a master pain blocker has been well researched, this is the first time it has been known to stimulate itching. To test the exact action of the chemical messenger, the researchers bred a strain of mice that lacked the genes to make serotonin. These and other normal mice were then injected with a substance that was known to produce itch. While the normal mice scratched away, these mice showed no signs of having itchy feelings.

Next, the scientists injected them with serotonin, and that’s when they scratched in response to the compound that gave them an itch.

"So this fits very well with the idea that itch and pain signals are transmitted through different but related pathways," Chen said. "Scratching can relieve itch by creating minor pain. But when the body responds to pain signals, that response actually can make itching worse."

But is blocking serotonin a solution to relieving humans from chronic itch? No, say the researchers, because serotonin is involved in much more important processes of growth, aging, and bone metabolism. It’s also a "feel good" hormone, and elevating levels of it has been shown to cure depression. Blocking serotonin might adversely affect the body, and people wouldn't have a natural way to control pain.

A better target would be the specific nerve cells that communicate itch signals to serotonin in the brain. Chen and his team worked on the cells known as GRPR neurons and isolated the receptor used by serotonin to activate them. The team accomplished this by injecting mice with itch-causing substances and at the same time activating various serotonin receptors on nerve cells. They found that the receptor known as 5HT1A was the key to activating the itch-specific GRPR neurons in the spinal cord.

By blocking the 5HT1A receptor, the mice scratched less, which further proved the involvement of the receptor in inducing the itch. "We always have wondered why this vicious itch-pain cycle occurs," Chen said. "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,” said Chen, adding that next time your mom suggests not scratching an itch, you should follow her advice. 

Source: Zhao Q, Liu Y, Jeffry J, et al. Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRPGRPR signaling. Neuron. 2014.