Isolated Merkel cell responding to touch. Image: Ellen Lumpkin / Columbia University Irving Medical Center

The Science Behind a Soft Caress

November 8, 2018

Touch – to scientists – remains our most enigmatic sense.

The cells and molecules underlying our senses of vision, hearing, smell, and taste have been known for 50 or more years, but the fundamental machinery used by mammals to detect touch is just beginning to be identified.   

“Our understanding of touch has been slow to emerge because the skin is innervated by a large variety of neurons that are built to trigger different sensations,” says neuroscientist Ellen Lumpkin, PhD, who studies mechanoreception at Columbia University Vagelos College of Physicians and Surgeons.

“But now new techniques that let us see individual components and turn entire cells on and off are accelerating our progress. These techniques are illuminating how a variety of skin cells are involved in touch and uncovering previously unknown mechanical receptors.”

 

Some Skin Cells Detect Gentle Touch

The Science Behind a Soft Caress

The skin’s sensory system is unique in that it gives rise to different sensations, including pain, itch, heat, vibrations, light pressure, and gentle touches.

Lumpkin’s lab has helped uncover the cells and molecules that detect gentle touch and send those signals to the brain.

Four years ago, they found that the skin’s Merkel cells – which are concentrated in our fingers and lips – are bona fide receptors for “gentle” touch. (The cells were first identified in 1875 and named “Taztzellen” or touch cells, but their function remained controversial for more than 130 years.)

Merkel cells are particularly important for fine motor skills. They help us detect the edges and textures of objects, as well as a soft caress or light pressure of a hand. Without Merkel cells, buttoning a shirt, using a fork, or typing an email would be difficult. 

The cells may also contribute to our cognitive development. Infants deprived of touch, other researchers have found, develop cognitive deficits that can persist into adulthood.

Malfunctioning Merkel cells may cause pain from gentle touch and contribute to itch. And the number of Merkel cells in our skin decreases with age, which may explain decreasing sensitivity to touch.

 

Latest Research Shows How the Brain Receives Touch Signals from the Skin

Though Lumpkin’s work established Merkel cells as bona fide touch cells, the sensation of a gentle touch isn’t perceived until the brain gets the message. 

But since Merkel cells are skin cells, not neurons, it was unclear how they could communicate with the nervous system.

With Merkel cells in mice, she and graduate student Benjamin Hoffman discovered that the cells send touch messages to neighboring neurons with an unusual neurotransmitter: norepinephrine. 

“False” fluorescent neurotransmitters helped allowed Hoffman see the Merkel cells in action and home in on norepinephrine. 

“After seeing the cells take up the fluorescent neurotransmitters – and release them when touched – we knew the cells sent touch signals with one of three neurotransmitters,” Hoffman says. “When we tested them one by one, only norepinephrine activated the neurons.”

Merkel cells (blue) in skin detect light touch. Image: Ellen Lumpkin / Columbia University Irving Medical Center
In the skin, Merkel cells (blue) detect light touch and transmit those signals to sensory neurons (red), which relay the signals to the brain. Image: Ellen Lumpkin / Columbia University Irving Medical Center.

 

Findings Suggest Beta Blockers May Impair Touch

With norepinephrine identified, the researchers turned their attention to the neurons receiving the neurotransmitters. The neurons, they found, pick up the neurotransmitters with beta-adrenergic receptors, which causes the neurons to send electrical signals to the brain.

The finding may explain why some people who take beta blockers – drugs that jam the receptors and are widely used to treat hypertension – experience numbness.

“It also suggests we may be able to treat pain and itch with a lotion that contains beta blockers, or treat loss of touch sensitivity with drugs that stimulate the receptors,” Lumpkin says.

“Ultimately, studies like this,” she adds, “have the power to lead us to new therapies that restore tactile sensitivity lost after injury or through aging, stop the pain that results when touch goes awry, and better understand the links between touch and our cognitive and emotional states.”

References

Ellen Lumpkin is associate professor of physiology & cellular biophysics and of dermatology at Columbia University Vagelos College of Physicians and Surgeons, and co-director, Thompson Family Foundation Initiative in CIPN & Sensory Neuroscience.

Benjamin U. Hoffman is a graduate student in the Doctoral Program in Neurobiology and Behavior at Columbia University.

The paper is titled, “Merkel Cells Activate Sensory Neural Pathways Through Adrenergic Synapses,” and was published online Nov. 8 in Neuron.

Other authors: Yoshichika Baba (Columbia University Irving Medical Center), Theanne N. Griffith (CUIMC), Eugene V. Mosharov (CUIMC), Seung-Hyun Woo (Scripps Research Institute), Daniel D. Roybal (CUIMC), Gerard Karsenty (CUIMC), Ardem Patapoutian (Scripps Research Institute and Howard Hughes Medical Institute), and David Sulzer (CUIMC).

This research was supported by grants from the National Institutes of Health (R01AR051219, F31NS105449, R01NS095435, R01MH108186, R01DA07418, T32GM007367, P30AR044535, and P30CA013696), Burroughs Wellcome Fund PDEP program, JPB Foundation, the Howard Hughes Medical Institute, and the Genomics Institute of the Novartis Research Foundation.

The authors declare no financial or other conflicts of interest.