CHICAGO, July 25 (Xinhua) -- Researchers at the University of Michigan (UM) have identified the neuronal pathway, from the skin to the spinal cord, responsible for transmitting mechanical itching sensation, opening the pathway for treating patients with chronic itch.
In the study posted on UM website on Wednesday, the researchers focused on nine distinct subsets of spinal neurons in the zone that those low-threshold mechanoreceptors innervate.
"To identify the mechanical itch transmission neurons, we individually ablated these nine subsets for their potential role in mechanical itch," said co-author Mahar Fatima, a postdoctoral research fellow at UM. "Behavioral analysis after the ablations of these neuronal subsets revealed that Ucn3 neurons are the mechanical itch transmission neurons whereas ablation of other spinal neurons did not affect the transmission of mechanical itch."
The researchers also discovered that a third component to the system, an inhibitory interneuron, called NPY inhibitory interneurons, controls the excitability of Ucn3 neurons or how much the tickling of the skin will cause you to itch.
To verify this neuronal circuit was responsible for mechanical itch, the researchers used several different techniques to manipulate the Ucn3 neurons. To trigger mechanical itch in mice, the researchers lightly tickled the mice behind the ear with a tool called a von Frey monofilament. The mice responded by scratching at their ears with the hind paw-scratching at the ear rather than rubbing at the ear indicates itch rather than pain.
In one line of mice, the researchers ablated the neuron. When the neuron was ablated, the mouse didn't respond to the tool's tickle.
Then, the researchers injected a chemical itching compound, which still induced the mouse to itch. This indicated that the neuronal pathways are separate, and that the ablated Ucn3 neurons are responsible for mechanical itch.
In another line of mice, the researchers used mouse genetics to silence the neuron. The mouse experienced the same effect: when Ucn3 neurons were silenced, the mouse didn't feel the mechanical itch. In each of these scenarios, these techniques did not affect the mice's ability to sense touch, pain or thermal sensation.
In addition, the researchers found that ablating the Ucn3 neurons in the spinal cord prevented the development of mechanical itch sensitization and persistent spontaneous itch in lines of chronic itch mouse models. They also found through electrophysiological study that under chronic itch conditions, the Ucn3 neurons lacked inhibition, or were more prone to being activated.
"Itching is one of the major symptoms in most skin disorders and other neurologic disorders," said Bo Duan, a researcher in the UM Department of Molecular, Cellular and Developmental Biology. "This is one mechanism we needed to understand to develop a new treatment for patients with chronic itch."
The research has been published in the journal Neuron.
