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You Scratch My Back ….

Why scratching an itch only makes it worse


It’s the sweetest relief… until it’s not.


Scratching an itch only gives temporary respite before making it worse – we now know why.


12:30 31 October 2014 by Colin Barras


Millions of people experience chronic itching at some point, as a result of conditions ranging from eczema to kidney failure to cancer.


The condition can have a serious impact on quality of life.


On the face of it, the body appears to have a coping mechanism: scratching an itch until it hurts can bring instant relief. But when the pain wears off the itch is often more unbearable than before – which means we scratch even harder, sometimes to the point of causing painful skin damage.


“People keep scratching even though they might end up bleeding,” says Zhou-Feng Chen at the Washington University School of Medicine in St Louis, Missouri, who has now worked out why this happens. His team’s work in mice suggests it comes down to an unfortunate bit of neural crosstalk.


We know that the neurotransmitter serotonin helps control pain, and that pain – from the heavy scratching – helps soothe an itch, so Chen’s team set out to explore whether serotonin is also involved in the itching process.


They began by genetically engineering mice to produce no serotonin. Normally, mice injected with a chemical that irritates their skin will scratch up a storm, but the engineered mice seemed to have almost no urge to scratch.


Genetically normal mice given a treatment to prevent serotonin leaving the brain also avoided scratching after being injected with the chemical, indicating that the urge to scratch begins when serotonin from the brain reaches the irritated spot.


The result helps explain why people can get hooked on scratching an itch to the point that they bleed, says Chen. “People scratch because the pain inhibits the itch,” he says – but because serotonin controls the pain, they then have to scratch harder to register pain strong enough to suppress the itch, creating a feedback loop. “The brain wants to control the pain so it puts out more and more serotonin.”

Ramping up the itch

But that’s not the end of it. A few years ago, Chen and his colleagues discovered that brain cells called GRPR neurons make the itch sensation stronger.


The team’s latest work on mice also shows that serotonin, on its way to the itch site, essentially gets its wires crossed and activates the itch-modulating GRPR neurons as well as pain-modulating neurons.


This means when we scratch an itch, the extra serotonin the brain releases to control the pain also aggravates the itchy sensation.


Chen says it should be possible to develop a therapy to control chronic itching by blocking the receptor through which serotonin activates the GRPR neurons. But Gil Yosipovitch, director of the Temple Itch Center at Temple University in Philadelphia, Pennsylvania, sounds a note of caution.


“The problem of chronic itch is that there not just one receptor and one pathway,” he says. “So there is long way to go from a nice mouse model to a therapeutic target.”

Journal reference: Neuron, DOI: 10.1016/j.neuron.2014.10.003

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