Neuroscientists Identify 16 Neuronal Types Involved in Human Sense of Touch

New research led by scientists from the University of Pennsylvania, Karolinska Institute and Linköping University provides a landscape view of the human sense of touch.

Humans perceive touch, temperature and pain through the somatic sensation system.

A common understanding is that there is a specific type of neuron for each type of feeling, such as pain, pleasant touch, or cold.

But a new study challenges that notion and shows that bodily sensations are probably much more complicated than that.

“Much of the knowledge we have today about how the nervous system works comes from research on animals,” said University of Pennsylvania’s Dr. Wenqin Luo and colleagues.

“But how big are the similarities between, for example, a mouse and a human?”

“Many findings in animal studies have not been confirmed in human research.”

“One reason for this may be that our understanding of how it works in humans is inadequate.”

“We wanted to create a detailed atlas of different types of neurons involved in human somatosensation and compare it with those of mice and macaques, a primate species.”

In the study, they made detailed analyses of the genes used by individual neurons, so-called deep RNA sequencing.

Neurons that had similar gene expression profiles were grouped together as one sensory neuron type.

In this way, the researchers identified 16 human-specific neuronal types.

The study is the first to link gene expression in different types of neurons with their actual function.

To investigate the function of neurons, the scientists used a microneurography technique to listen to the signaling in one neuron at a time.

Using this technique, they can subject skin neurons in awake participants to temperature, touch or certain chemicals, and ‘listen in on’ an individual neuron to find out if that particular neuron is reacting and sending signals to the brain.

During these experiments, the authors made discoveries that would not have been possible, had the mapping of the cellular machinery of different types of neurons not given them new ideas to test.

One such discovery concerns a type of neuron that responds to pleasant touch.

The researchers found that this cell type unexpectedly also reacts to heating and capsaicin, the substance that gives chili its heat.

Reacting to capsaicin is typical of pain-sensing neurons, so it surprised the scientists that touch-sensing neurons responded to such stimulation.

Further, this neuronal type also responded to cooling, even though it does not produce the only protein so far known to signal cold perception.

This finding cannot be explained by what is known about the cell’s machinery and suggests that there is another mechanism for detection of cold, which has not yet been discovered.

The authors speculate that these neurons form an integrated sensory pathway for pleasant sensations.

“For ten years, we’ve been listening to the nerve signals from these neurons, but we had no idea about their molecular characteristics,” said Linköping University’s Dr. Håkan Olausson.

“In this study, we see what type of proteins these neurons express as well as what kind of stimulation they can respond to, and now we can link it. It’s a huge step forward.”

Another example is a type of very rapidly conducting pain-sensing neuron, which was found to respond to non-painful cooling and menthol.

“There’s a common perception that neurons are very specific — that one type of neuron detects cold, another senses a certain vibration frequency, and a third reacts to pressure, and so on,” said Dr. Saad Nagi, also from Linköping University.

“It’s often talked about in those terms. But we see that it’s a lot more complicated than that,”

And what about the comparison between mice, macaques and humans? How similar are we? Many of the 16 types of neurons that the researchers identified in the study are roughly similar between the species.

The biggest difference they found was in very rapidly conducting pain-sensing neurons that react to stimulation that can cause injury.

Compared to the mouse, humans have many more pain neurons of the type that send pain signals to the brain at high speed.

“Why this is so, our study cannot answer, but we have a theory,” Dr. Olausson said.

“The fact that pain is signaled at a much higher velocity in humans compared to mice is probably just a reflection of body size.”

“A mouse doesn’t require such rapid nerve signaling. But in humans, the distances are greater, and the signals need to be sent to the brain more rapidly; otherwise, you’d be injured before you even react and withdraw.”

The research is described in a paper in the journal Nature Neuroscience.

_____

H. Yu et al. Leveraging deep single-soma RNA sequencing to explore the neural basis of human somatosensation. Nat Neurosci, published online November 4, 2024; doi: 10.1038/s41593-024-01794-1