Sensory Neuron Discovery Could Lead to Novel Pain Treatments

Researchers have discovered a new, unique type of sensory neurons in mice that can be activated by stimuli as isolated as the pulling of a single hair. Understanding these different responses is expected to lead to novel approaches to treating pain in humans, according to a study published by Neuron.

“Scientists know that distinct types of neurons detect different types of sensations, such as touch, heat, cold, pain, pressure, and vibration,” said lead author Alexander Chesler, PhD. “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 the study, the authors analyzed functional imaging, recordings of electrical activity in the brain, and genetics to determine how neurons respond to stimuli. The investigators focused on sensory neurons that express the Calca gene.

The authors explored the effects of gentle mechanical stimuli (air puff, stroking, and brushing) and high-threshold mechanical stimuli (hair pulling and skin pinching), and temperature on the cheek skin of mice, according to the study.

They found that the neurons involved were part of 2 categories that are unaffected by gentle stimulation. The first was the well-known polymodol nocicpetor, which responds to high-intensity stimuli. The second was a previously unknown type of high-threshold mechanoreceptor HTMR), which responds to hair pulling, called circ-HTMRs.

The authors found that endings of the nerve fibers created a lasso-like structure around the hair follicles in mice.

“One interesting feature of these neurons is that they have large spatially organized receptive fields, yet can be activated by pulling a single hair,” Dr Chesler said. “Their electrical properties enable them to signal much more rapidly than normal pain fibers and to keep firing as long as the hair is being pulled.”

In further studies of circ-HTMRs, the authors found that the direct activation of the receptors was linked to the onset of protective behaviors, according to the study.

The investigators hypothesize that these findings could lead to additional knowledge about pain, which would result in better treatments.

“These findings add insight into how the somatosensory system encodes pain,” said Josephine Briggs, MD, director at NCCIH. “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.”