The magic touch

Touch has always been the poor cousin among the five senses that human beings possess, despite being the first to develop. Perceptible to the foetus within eight weeks of pregnancy, touch allows humans to detect and process tactile information inside and outside the body. But research on touch lags behind work on other sensory systems.

Human beings perceive touch, pressure, temperature, and pain through the somatic sensory system, a network of neurons. These somatosensory neurons that innervate the skin help people sense mechanical, chemical, and thermal stimuli, which are processed in the central nervous system to generate perceptions.

Much of the prevailing knowledge on touch comes from research on animals. However, not all findings from animal studies have been confirmed in humans. Now, researchers from Sweden and the U.S. have discovered that 16 different types of nerve cells are involved in processing human touch. Their study, published in Nature Neuroscience in November (bit.ly/sense-touch), compared the human somatosensory system with that of mice and a primate model, the macaque, unearthing several similarities and significant differences between them. The study was conducted by researchers from Swedish institutions Linköping University and Karolinska Institutet, and the University of Pennsylvania.

"This is the first single-cell RNA sequencing on the soma (the cell body of a neuron in the brain) of human peripheral nerve cells," says Håkan Olausson, Professor at Linköping University and one of the study's main authors. He adds that a pioneering technique developed by a team led by Wenqin Luo, a neuroscientist at UPenn's Perelman School of Medicine, made the study possible. Her team used laser technology to dissect the soma of individual dorsal root ganglion (DRG) cells. DRG cells are the primary sensory neurons in the peripheral nervous system that transmit sensory information from the body to the spinal cord.

Using this technique, the scientists sequenced over 1,000 human DRG neurons gathered from six lower thoracic and lumbar regions of three volunteers. They found that each of these neurons had expressions of approximately 9,000 unique genes. They analysed the genes used by individual nerve cells. Nerve cells with similar gene expression profiles were grouped as one sensory nerve cell type. This led to the identification of 16 distinct nerve cell types. "There is a substantial overlap of genes across nerve cells. However, most of the different cell types had some unique gene expression," says Olausson. "For ten years, we've been listening to the nerve signals from these nerve cells, but we had no idea about their molecular characteristics." The study shows what type of proteins these nerve cells express and stimulations they can respond to. "It's a huge step forward," Olausson says.

Arnab Barik, Assistant Professor at the Centre for Neuroscience, Indian Institute of Science, Bengaluru, agrees. "This study will have a significant impact on... the understanding of the neurobiology and treatments of pain," he says. The comparison with similar somatosensory systems of mice and macaques showed that many properties of such systems were highly conserved across the species. But they also identified some human-specific nerve cell types. "One surprising finding was that humans have many more types of fast-conducting nociceptors (nerve endings that trigger pain sensations) than mice and macaques," Olausson says. Pain is signalled at a much higher velocity in humans than in mice, which may be a reflection of body size. A mouse doesn't require such rapid nerve signalling. "In humans, the signals need to be sent to the brain more rapidly; otherwise, you'd be injured before you even react and withdraw," he says.

A myth shattered by this study is the prevailing perception that each nerve cell type has a specific function: one type of nerve cell detects cold, another senses pressure, etc. The scientists found the workings of the nerve cell types were much more complex. They are now planning more in-depth studies to make "portraits" of different types of nerve cells they have identified.