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The researchers first injected itch-inducing histamine into the mice. Both the normal and knockout mice behaved similarly, scratching furiously. But when the researchers injected chloroquine, the mice lacking Mrgpr genes scratched less—nearly three times less often than normal mice.
“Now, we think these receptors function as novel itch receptors, like the histamine receptor,” says Dong.
It can't be said yet whether the receptors respond to other forms of nonallergic itch, like that associated with psoriasis or poison ivy; Dong's lab is testing that question. But the discovery helps get to the root of a sensation about which there's heated debate, says Dong.
“Some people propose that itch is the little brother to pain,” explains Dong. “If you get a little bit of the sensation, you get the itch, if you get a lot, you feel pain.” Another possibility is that there are distinct nerve cells—those dedicated to itch, different ones for pain, and others for ordinary touch.
Dong proposes a third view. “We think that these two circuitries are not really separate, but the pain circuitry is much larger. If you activate a large population of pain-sensing neurons, you get pain. The itch-sensing neurons reside within a subset of pain-sensing neurons, and if you activate them specifically you get itch sensation,” he says.
“The big prize here would be to find the population of neurons that respond to multiple nonhistaminergic, itch-inducing compounds and find a drug that shuts those cells down,” says Anderson.
And he has a daily reminder of the relief that such a drug could bring: his cat. “She has a chronic itch problem; she just tears acres of fur off her head and her neck,” he says. The only treatment is steroids, and Anderson's veterinarian has warned that continued steroid exposure could create its own health issues for the animal. “People have underestimated the importance of itch because it's not a life-threatening condition like cancer or Alzheimer's disease. But it has a huge impact on the quality of life.”