Scratch That Theory: Itchiness and Pain May Not Share the Same Sensory Pathway

What do itch and pain have in common? Maybe less than researchers previously thought. A team of scientists is learning more about the "itch gene" and how it works separately from pain pathways

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An annoying mosquito bite might feel a lot different to us than a painful bee sting, but scientists have long debated the relationship between itch and pain, as the two sensations have often been thought to use some of the same sensory pathways.

But new research, published today in Science, reveals that—at least in mice—itch and pain do, in fact, use different neurons and possibly even different cellular pathways.

Zhou-Feng Chen, an associate professor of developmental biology, psychiatry and anesthesiology at Washington University in Saint Louis, had been part of a group that first discovered the gene that allows mice to feel itchiness (GRPR or gastrin-releasing peptide receptor) in 2007. But at the time it was unclear whether this gene, expressed in neurons located in the spinal cord, was also involved in transmitting painful sensations. "We know itch and pain are two different sensations, so as scientists we are trying to find out how they are different," Chen explains.

So to test whether the itch gene was also involved in pain transmissions, Chen and his team tried inactivating the gene in a group of mice. Previous researchers had tried using electrophysiology to pinpoint how these sensations work, but Chen says it was important to him to alter the genes and then "check the behavior response very, very comprehensively," he says.

As predicted, mice that had their GRPR gene deactivated (by killing neurons where it was expressed) would not scratch when exposed to an itchy stimulus. Furthermore, killing these itch-tuned neurons did away with both histamine-dependent itching (short-term, such as that from a bug bite) and chronic, long-term itchiness (as might occur from a disease, such as eczema or psoriasis).

But what amazed Chen and his colleagues was that these mice still responded with normal reaction times to pain stimuli, such as dipping their tails in hot or cold water or pressing on their paws. The GRPR gene, at least, didn't seem to have any other effects on the mice other than toning down their itchiness sensation.

Will these findings translate to other members of the animal kingdom? Chen is optimistic: "No matter if it's a dog, cat—they all scratch. We think that the scratching response is universal." But, he cautions, "we don't know whether humans have this kind of sensory neuron or not." If the relationship does prove to be the same in people, the discovery could help researchers develop more effective treatments for our chronic itching.

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