Specialized Mouse Neurons Play a Unique Role in Pain

Mouse on a hamster wheel

Researchers from NIH have identified a class of sensory neurons (nerve cells that electrically send and receive messages between the body and brain) that can be activated by stimuli as precise as the pulling of a single hair. Understanding basic mechanisms underlying these different types of responses will be an important step toward the rational design of new approaches to pain therapy. The findings were published in Neuron.

“Scientists know that distinct types of neurons detect different types of sensations, such as touch, heat, cold, pain, pressure and vibration,” said Dr. Alexander Chesler, lead author of the study and principal investigator with NCCIH. “But they know more about neurons involved with temperature and touch than those underlying mechanical pain, like anatomical pain related to specific postures or activities.”

In this study, Chesler and his colleagues used a novel strategy that combined functional imaging (which measures neuronal activity), recordings of electrical activity in the brain and genetics to see how neurons respond to various stimuli. The scientists focused on a class of sensory neurons that express a gene called Calca, as these neurons have a long history in pain research.

The scientists applied various stimuli to the hairy skin of mice cheeks, including gentle mechanical stimuli (air puff, stroking and brushing), “high-threshold” mechanical stimuli (hair pulling and skin pinching) and temperature stimulation. They found that the target neurons belong to two broad categories, both of which were insensitive to gentle stimulation. The first was a well-known type of pain fiber—a polymodal nociceptor—that responds to a host of high-intensity stimuli such as heat and pinching. The second was a unique and previously unknown type of neuron that responded robustly to hair pulling. They called this previously undescribed class of high-threshold mechanoreceptors (HTMRs) “circ-HTMRs,” due to the unusual nerve terminals these neurons made in skin. They observed that the endings of the fibers made lasso-like structures around the base of each hair follicle.

“These findings add insight into how the somatosensory system encodes pain,” said NCCIH director Dr. Josephine Briggs. “Learning more about the distinctive features of circ-HTMRs could contribute to rapid, accurate localization of brain regions activated in mechanical pain, and ultimately to the rational design of new approaches to pain therapy.”