Specialized Mouse Neurons at Heart of Pain Study

Illustration of hair follicles. (Image credit: Jeremy and Nichole Swan)

BETHESDA, Md. (CN) – Most people know how pulling a single hair causes pain. The National Institutes of Health shed light on the why Wednesday, announcing the discovery of a previously unknown class of sensory neurons.

Reporting on a study published in the journal Neuron, the NIH says the research team used a novel strategy that combined imaging of neuronal activity, recordings of electrical activity in the brain and genetics to see how neurons respond to various stimuli.

“Scientists know that distinct types of neurons detect different types of sensations, such as touch, heat, cold, pain, pressure, and vibration,” Alexander Chesler, the lead author of the study, told the NIH. “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.”

Chesler’s team focused on a class of sensory neurons that express a gene called Calca, as these neurons have a long history in pain research.

Using furry cheek skin from mice, the scientists applied various stimuli ranging from gentle brushing to hair pulling and skin pinching, as well as temperature stimulation.

Unlike with gentle stimulation, one of the target neurons, a polymodal nociceptor, proved sensitive to a host of high-intensity stimuli such as heat and pinching.

While researchers are familiar with the polymodal nociceptor, they said the second targeted neuron was a unique and previously unknown type that responded robustly to hair pulling.

Citing the unusual nerve terminals these neurons made in skin, they christened this discovery “circ-HTMRs,” short for high-threshold mechanoreceptors.

In addition to observing that the endings of the fibers made lasso-like structures around the base of each hair follicle, the researchers found that direct activation was sufficient to drive protective behaviors, such as avoiding a chamber paired with blue light stimulation.

“One interesting feature of these neurons is that they have large spatially organized receptive fields, yet can be activated by pulling a single hair,” said Chesler, who is principal investigator with the National Center for Complementary and Integrative Health’s Division of Intramural Research. “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.”

Josephine Briggs, who is director of the center where Chesler works, said the study sheds light on how the somatosensory system encodes pain.

“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,” Briggs said, as quoted by the NIH.

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