Research published in Cell Reports from the University of Alabama at Birmingham reveals that, by labeling a subset of trigeminal afferents with the genetic marker Fos-Cre and inhibiting them, researchers were able to identify a correlation between the activation of these neurons and the pain sensory condition called mechanical allodynia.
Trigeminal afferents are primary sensory neurons located in the trigeminal ganglion. These nerves are responsible for receiving pain, itch and touch sensation signals in the face and transporting them to the brain. Mechanical allodynia is the condition that refers to painful nerve responses to delicate or a seemingly non-impactful stimulus after recovery from nerve damage. Previously non-painful stimuli become painful after injury or inflammation. This condition is commonly caused after a trigeminal nerve injury occurs.
The study findings signify the ability to target and inhibit the neurons, thus providing a potential remedy from pain associated with the condition.
Study author and primary investigator Yu Shin Kim, Ph.D., Presidential Faculty Scholar Professor and professor in the Department of Endodontics in UAB School of Dentistry, says this research has established an understanding that can inform the future of craniofacial and dental pain management.
“Mechanical allodynia has been a major clinical problem, but research has not clearly understood which nerve cells were responsible until now,” Kim said. “Our study identifies those cells and shows they play a direct role in driving pain.”
Developments could lead to more targeted treatment options for individuals dealing with pain from severe trauma, dental injuries or things such as car accidents.
Piezo2 is an ion channel protein that is integral in the reception of sensory touch. This allows the physical surface stimulants to be translated into nerve sensations.
“If we knock down the Piezo2 ion channel, which is responsible for the mechanical sensation in humans, we can reduce the pain experience,” Kim said. “Using this model, we can translate the data to human patients to focus on the subset of receptors that are responsible.”
In identifying the trigeminal afferents responsible, Kim and the research team, composed of researchers from UAB, University of Maryland, Johns Hopkins School of Medicine and Hallym University, were able to identify the neurons that were activated by facial brushing in mouse models.
“This fundamental understanding establishes a framework for understanding how this subset of afferents can drive pain in humans,” Kim said.
The trigeminal ganglion is home to reception of primary sensory neurons in the face and can sense all forms of touch, itch and pain. Facial brushing activates certain fibers in which Fos-Cre labels the activated afferents.
Utilizing a chemogenetic trap, or targeted recombination in active populations, a methodology was revealed to target responsible sensory neurons that signal pain in the same way. Inhibiting these responding neurons could alleviate mechanical allodynia since these neurons signal for pain when trauma has caused neurons to become inflamed or damaged and become hypersensitized.