New research uncovers vicious scratch-itch cycle

Scratching results in the brain’s release of serotonin, intensifying the itch sensation, according to results of a recent animal study. Understanding how to better control the cycle could lead to less itching, especially in those suffering from chronic itching.

Scientists have long known that scratching creates mild pain in the skin, which can temporarily interfere with the itch. Researchers at Washington University School of Medicine, St. Louis, sought to look more closely at the itch cycle. 

“The problem is that when the brain gets those pain signals, it responds by producing the neurotransmitter serotonin to help control that pain,” senior investigator Zhou-Feng Chen, Ph.D., director of Washington University’s Center for the Study of Itch, said in a news release. “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.”

Dr. Chen and colleagues bred mice without serotonin-making genes and found the genetically engineered mice didn’t scratch as much as normal mice when injected with a substance that makes the skin itch. But when injected with serotonin, the genetically altered mice responded to the induced skin itch like normal mice.

The problem is interfering with serotonin release is not practical in humans. Rather, Dr. Chen says an option for dermatology and other patients might be to interfere with GRPR neurons, which relay itch signals from the skin to the brain.

The research team used the mouse model to isolate the receptor used by serotonin to activate GRPR neurons, discovering the 5HT1A receptor was the key to activating the itch-specific GRPR neurons in the spinal cord. When they treated mice with a compound that blocked the 5HT1A receptor, scratching diminished.

They discovered that initially, scratching causes a pain sensation. The increase in serotonin to control pain also intensifies itch by activating GRPR neurons through 5HT1A receptors.

Brian S. Kim, M.D., assistant professor of medicine (dermatology) at Washington University and a faculty member in the Center for the Study of Itch but not an author on the study, tells Dermatology Times, “There are currently no FDA (Food and Drug Administration)-approved treatments for chronic itch which is a widespread and highly debilitating medical problem. One striking phenomenon in patients with chronic itch related to eczema is that they will scratch even though they bleed and create skin lesions that would typically be quite painful for most healthy individuals.

“Dr. Chen’s findings explain how serotonin released from the act of scratching may actually simultaneously override the sensation of pain and result in more itch as observed in our eczema patients,” Dr. Kim says. “Importantly, this study highlights a previously unrecognized serotonin pathway in mediating itch and may represent a novel therapeutic target in patients.”

The study findings were published online Oct. 30 in the journal Neuron.