Chronic pain and itch affect about one in 10 Americans. A better understanding of pain and itch signals' journey to the
brain may lead to new treatment options, eventually.
There are neurons in your skin that are wired for one purpose and one
purpose only: to sense itchy things. These neurons are separate from
the ones that detect pain, and yet, chemical-induced itch is often
accompanied by mild pain such as burning and stinging sensations.
‘The spinal cord neurons receiving the peripheral pain and itch inputs are not separate. They can receive signals from itch fibers and also pain fibers.’
when it comes to sending signals toward your brain through your spinal
cord, itch and mild pain can go through the same set of spinal cord
neurons, researchers report in Neuron
. This finding explains why pain often accompanies intense chemical-induced itch.
"To our surprise, we found the spinal cord neurons receiving the
peripheral pain and itch inputs are not separate. They can receive
signals from itch fibers and also pain fibers," says study coauthor and
neuroscientist at Johns Hopkins University Xinzhong Dong. These
neurons, called the GRP neurons, are a way station for pain and itch
signals on their way to the brain.
However, GRP neurons are not passive conduits, the researchers
found. "When we eliminate this population of neurons in mice, the itch
response is reduced. They scratch less," says the study's first
co-author Shuohao Sun, a graduate student at Hopkins. "But at the same
time, the pain response is actually increased."
Mice without GRP neurons spent more time rubbing and licking to
alleviate their pain, induced, for example, by exposing their tails to
hot water. Further experiments that tracked electrical signaling through
the neurons corroborated the result. Even though the GRP neurons seemed
to be forwarding mild pain signals to the next neural relay station,
they also seemed to mitigate intense pain signals.
"It might sound counterintuitive, but we suggest that this small
group of cells actually functions like a braking system for pain," says
Sun. "This brake is not always triggered by the painful stimuli; it's
only triggered by the strong pain stimuli. When the brake is on, the
signal doesn't go through. But when you have a weak pain signal, it
doesn't trigger the brake and the signal can go through." The
researchers have named this hypothesis "the leaky gate" model.
When the mice's GRP neurons have been destroyed, the brake lines
have essentially been cut, resulting in an uncontrolled cascade of pain.
The braking system may be a way for animals to detect mild pains--like
the kinds associated with itchy substances - without becoming overwhelmed
by the pain, the researchers say. Built-in pain management would likely
be a helpful adaptation for escaping from predators while injured.
At the same time, GRP neurons are not the only group of spinal cord
neurons that receive and forward pain signals toward the brain, and the
brain itself plays a central role in translating signals from peripheral
neurons into experienced sensation. Questions remain about what happens
to the signals from GRP neurons after they're transported up the spinal
"The next step is
moving even further into the central nervous system and seeing how the
signal from the secondary neuron is getting to the next relay station,"
says Dong. "We go one step at a time."