To scratch an itch is to scratch many itches: placing nails to skin brings sweet yet short-lived relief because it often instigates another bout of itchiness. The unexpected culprit behind this vicious cycle, new research reveals, is serotonin, the so-called happiness hormone.

Scientists thought itch was merely a mild form of pain until 2009, when Zhou-Feng Chen and his colleagues at the Center for the Study of Itch at Washington University in St. Louis discovered itch-specific neurons in mice. Though not identical, itch and pain are closely related; they share the same pathways in certain brain areas. Because of the doubling up, activating one suppresses the other, which is why scratching blocks the itch sensation momentarily. The act, however, also triggers the release of the chemical serotonin, which helps to alleviate pain. It is that burst that makes scratching feel good, but recent work by Chen's group showed that it exacerbates the itch-scratch cycle, too.

Itch-sensing neurons have a set of receptors that facilitates pain relief and another that induces itch. Serotonin can bind only to the pain-related receptor, but because the two sets sit close to each other and physically interact, the chemical's arrival indirectly enhances the itch pathway. When Chen and his colleagues activated both receptors simultaneously in mice, the rodents scratched much more than if the itch-inducing receptor was turned on alone. In another experiment, mice lacking the cells that produce serotonin scratched less than normal mice when exposed to a skin irritant. The findings were published in the journal Neuron.

Scientists have yet to locate itch-specific neurons in humans (macaques have them). For now it is safe to say: think twice before you twitch to the itch.