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How the nervous system perceives pleasant touch

Grooming and other forms of pleasant touch can have many beneficial effects for animals, including people.tilialucida / Shutterstock

For social animals like people, touch is vital. Pleasant touch, such as hugging, cuddling, or holding hands, can provide a positive emotional boost, reduce stress, and strengthen social bonds.

But more is known about how the nervous system processes unpleasant sensations like pain and itch than pleasant touch. Studies have previously identified some types of nerve cells that seem to play a role in sensing positive touch. But how the sense of positive touch is transmitted to the brain hasn’t been understood.

In a new study, an NIH-funded research team led by Dr. Zhou-Feng Chen from Washington University in St. Louis used mice to explore the role of a molecule called prokineticin receptor 2, or PROKR2, in transmitting the sensation of pleasant touch. PROKR2 is a receptor found on the surface of some types of nerve cells. The researchers had identified PROKR2 by searching for all receptors on neurons in part of the spinal cord involved in sensory perception. Results of the study were published on April 29, 2022, in Science.

When the team engineered mice to lack PROKR2 or the signaling molecule that binds to it—a neuropeptide called PROK2—the mice didn’t lose the ability to sense pain or itch. But testing whether PROKR2 nerve-cell signaling affected their ability to enjoy pleasant touch was more difficult. Like humans who don’t like being touched by a stranger, mice don’t normally like to be handled by people or touched by an unfamiliar object.

To overcome this obstacle, the team slowly conditioned the mice to accept gentle stroking with a brush. This provides a pleasant sensation akin to being groomed by another mouse. Then, the researchers let the mice choose between two chambers in a cage: one where they would receive gentle stroking and one without touch.

Normal mice with PROK2 and PROKR2 developed a preference for the chamber where they received gentle stroking. In contrast, mice engineered to lack PROKR2 or PROKR2 in their spinal neurons did not. When the researchers used a technique called optogenetics to control when PROKR2 neurons were turned on, the mice preferred chambers in which those neurons were activated. These findings suggested that signaling driven by PROK2 and PROKR2 is required for the mice to enjoy pleasant touch, and that activation of PROKR2 neurons is rewarding.

The team also found that normal mice showed signs of reduced stress while being stroked, such as a lowered heart rate and drops in blood hormones related to stress. In contrast, mice lacking PROKR2 didn’t show reductions in stress from pleasant touch.

Technology that could record the activity of neurons in living mice showed that neurons with PROKR2 responded strongly to gentle stroking at a medium speed but less so at a slower or faster speed. This is similar to a pattern seen in sensory fibers called C tactile fibers, which are responsible for sensing pleasant touch in human skin.

In a final set of experiments, mice lacking PROKR2 from birth displayed more stress in response to changes in their environment. They also lacked normal social behaviors, such as curiosity about a new mouse or social grooming. Deficiencies in signaling controlled by PROK2 and PROKR2 could potentially play a role in social isolation, anxiety, and some developmental disorders.

"Now that we know which neuropeptide and receptor transmit only pleasant touch sensations, it may be possible to enhance pleasant touch signals without interfering with other circuits, which is crucial because pleasant touch boosts several hormones in the brain that are essential for social interactions and mental health,” Chen says.

—by Sharon Reynolds