Johns Hopkins: 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. But 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 Feb. 22 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 Xinzhong Dong, Ph.D.,
professor of neuroscience at the Johns Hopkins University School of
Medicine and Howard Hughes Medical Institute investigator, who led the
study. 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 first author Shuohao Sun, a
graduate student at Johns 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
At the same time, GRP neurons are not the only group of spinal
cord neurons that receive and forward pain signals to 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 cord.
Chronic pain and itch affect about one in 10 Americans, the
authors say. A better understanding of pain and itch signals’ journey to
the brain may eventually lead to new treatment options. “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.” – text courtesy of Cell Press
Other authors on the paper are Qian Xu and Yun Guan of the Johns
Hopkins University School of Medicine, and Changxiong Guo and Qin Liu of
Washington University School of Medicine.
This work was supported by the National Institute of Dental and
Craniofacial Research (grant number R01DE022750) and the National
Institute of Neurological Disorders and Stroke (grant number