"The (pain) braking system- the leaky gate model"

"The (pain) braking system- the leaky gate model"
Credit: Neuron

There are neurons in our  skin that are meant for the purpose to sense itch.  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 our brain through the spinal cord, itch and mild pain can go through the same set of spinal cord neurons. This study finding explains why pain often accompanies intense  chemical- induced itch.

It was found that, the spinal cord neurons receiving the peripheral pain and itch inputs are not separate.  They can receive signals from  both itch fibers and pain fibers, says a study coauthor. These spinal intereurons, called the  gastrin- releasing peptide (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. However, when the Grp neurons are eliminated in mice, the itch response is reduced, but at the same time, the pain response is increased.

Mice without Grp neurons spent more time rubbing and licking to alleviate their pain, induced. 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 alleviate 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 the first co- author of the study. "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.

A better understanding of pain and itch signals' journey to the brain may lead to new treatment options. The next stage of the study should be into the central nervous system to see how the signal from the secondary neuron  gets to the next relay station, comments the co-author of the study.