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Big Question: Why Does Scratching Make You Itch More?
皮肤越挠越痒，到底是怎么回事？

Hell is an itch that can’t be scratched.If you’ve ever had one under a cast or on an otherwise inaccessible body part, perhaps you can relate.

The good news is that most earthly itches are in fact scratchable.Scratching may provide temporary relief, but it also promotes more intense itching, which makes you scratch harder.

Scientists call this the itch-scratch cycle, and they’ve only recently started to understand why it’s so hard to resist.

Itch was considered nothing more than a subset of pain — a sort of “pain lite” caused by low-level activation of pain neurons.But while the two sensations do share many of the same nervous system pathways, new research has shown that itch has its own dedicated nerve cells, molecules, and cellular receptors.

At least starting in the skin level, there seems to be a separate itch pathway and a separate pain pathway.It’s basically two different circuits, but the two circuits can still interact.

Those interactions are what Zhou-Feng Chen, a developmental biologist and the director of Washington University’s Center for the Study of Itch, wanted to better understand back in 2007.

That’s when he and a group of researchers accidentally stumbled across a small group of nerve cells in the spinal cord that seemed to specifically transmit itch signals.
Their work led to the discovery of the first “itch gene,” GRPR (gastrin-releasing peptide receptor), which seemed to be key in relaying itch signals (and only itch signals) from the spine to the brain.

Chen’s research group took a batch of genetically altered mice without the GRPR gene, and then they made them itch.Not with tiny mouse-sized sweaters, but with injections of a histamine-promoting substance called compound 48/80.

The mice without GRPR scratched far less than mice that had it, says Chen.At the same time, though, both sets still responded to pain.

Chen knew that scratching seemed to relieve itching by getting nerve cells in the spinal cord to transmit pain signals to the brain instead of itch signals.What he didn’t foresee was that the brain’s response to those pain signals could also exacerbate the itch-scratch cycle.
In a subsequent paper published in the journal Neuron, Chen and his co-authors showed that when mice scratch, the brain produces the neurotransmitter serotonin.

As the pain-reducing signal spreads from the brain to the spinal cord, it seemed to jump from pain-sensing neurons to the nerve cells that influence itch intensity, he says.Specifically, those itch-specific GRPR ones.

“What people didn’t know is that when serotonin is produced by the pain and goes into the spinal cord, it actually makes the GRPR neurons a lot more active, and you a lot more itchy,” Chen says.