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Discovered: The Molecule Responsible for Itchiness

A neurotransmitter called Nppb, we now know, plays a vital role in the sensation of an itch—and removing it can prevent itchiness entirely

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A neurotransmitter called Nppb, we now know, plays a vital role in the sensation of an itch—and removing it can prevent itchiness entirely. Image via Wikimedia Commons/Orrling

There’s a lot we don’t understand about an itch. Why do itches sometimes pop up for no apparent reason? Why is itching contagious? Why can the very idea of an itch—maybe even the fact that you’re currently reading about itching—cause you to feel the actual physical sensation of one?

Given all this uncertainty, a new discovery reported today in Science should at least scratch the surface of your curiosity and answer a question you’ve been itching to ask (terrible puns intended). A pair of molecular geneticists from the National Institutes of Health, Santosh Mishra and Mark Hoon, isolated a crucial signaling molecule produced by nerve cells that is necessary for passing along the sensation of an itch to the brain.

The pair worked with mice, and started off by examining the neurotransmitter chemicals produced by a type of neuron that runs all the way from the animals’ skin into their spinal columns. These neurons are known to be involved in passing along sensory information about the outer environment, including sensations of heat and pain. They measured that one of the neurotransmitters produced by these nerve cells—a chemical called Nppb (natriuretic polypeptide b)—was secreted in excess when the mice were subjected to a range of itch-inducing substances, such as histamine (the natural compound that triggers the itchiness associated with allergies) and chloroquine (a malaria drug that’s notorious for causing itching as a side-effect).

To test whether Nppd played a role in the itching, they genetically engineered some mice so that they failed to produce the chemical. Initially, they checked to see if these engineered mice were impervious to other types of sensations also conveyed by these neurons (pain, movement and heat), but they seemed to behave just the same as the normal mice, indicating Nppb wasn’t involved in the transmission of those stimuli.

Then, they exposed them once again to the itch-inducing chemicals. The normal mice scratched away, but the genetically engineered mice were another story. “It was amazing to watch,” Mishra said in a press statement. “Nothing happened. The mice wouldn’t scratch.”

Nppb, they determined, plays a key role in passing along the sensation of an itch from these neurons to the brain—especially because, when they injected these same mice with doses of Nppb, they suddenly started scratching just like the others.

To investigate just how Nppb relays this message, they zeroed in on a spot in the mice’s spines called the dorsal horn, in which sensory information from the skin and muscles gets integrated into the spinal column and sent to the brain. In this area, they discovered a high concentration of neurons with a receptor called Npra (natriuretic peptide receptor A) that seemed likely to accept the Nppb molecules secreted when the mice encountered an itch-triggering substance.

Sure enough, when they removed the neurons with the Npra receptor from normal, non-engineered mice that produced Nppb, they too stopped scratching when exposed to the substances. This indicates that Nppb is crucial for passing along the itch sensation from the nerves that reach out into the skin to the spine, and that it fits into the Npra receptor on spinal nerve cells, which then convey the sensation to the brain. But removing these receptors didn’t impact the transmission of pain or touch, indicating that Npra is specifically involved in the itch sensation pathway. This comes as a surprise, as most previous research has indicated that the pain and itching nervous networks are intricately related.

While this chemical pathway explains part of the physical mechanism behind an itch, scientists still don’t fully understand the underlying evolutionary reason for the sensation in the first place. Some have speculated that it serves as a defense measure against insects, parasites and allergens, prompting us to scratch—and, ideally, remove the offending item from our skin—before it causes further damage.

Regardless of the evolutionary reason, our nervous system is similar enough to that of mice that the finding could help us better understand itching patterns in humans—perhaps people who are more prone to itching naturally produce higher levels of Nppb, compared to those who get biten by a mosquito and find the itchiness easy to ignore. On a practical level, the discovery could eventually help us develop anti-itch drugs for people with chronic itching ailments, such as allergic reactions or skin conditions like eczema, which affects an estimated 30 million people.

The problem, though, is that Nppb plays several other important roles in the body (it was originally discovered due to its role in the regulation of blood circulation and pressure) so simply creating a drug that disables Nppb is likely to cause disruptive side-effects that go way beyond itching. But looking more closely into the way the Nppb molecule acts as a “start switch” for itching in humans—and perhaps figuring out a way to safely turn the switch off—could potentially provide relief for itchiness caused by all sorts of triggers, because in the mice, at least, the molecule was found to be involved in the whole range of itch-inducing substances the team tested.

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