Researchers at the Washington University School of Medicine in St. Louis are uncovering how the body transmits the sensation of pleasant touch from the skin to our brains — at least, how mice’s bodies do it.

Who here doesn’t love a gentle caress? Known as ‘soft touch’, this type of physical stimuli is known to shore up our emotional state and protect our mental health and overall balanced development. But exactly how this sensation is transmitted through the body was not known. Finding out more about the nerve circuits and neuropeptides — chemical messengers that carry signals between nerve cells — that carry this sensation between the skin and the brain can help researchers understand and treat disorders that involve touch avoidance.

Getting pats

“Pleasant touch sensation is very important in all mammals,” said principal investigator Zhou-Feng Chen, PhD, director of the Center for the Study of Itch & Sensory Disorders at Washington University. “A major way babies are nurtured is through touch. Holding the hand of a dying person is a very powerful, comforting force. Animals groom each other. People hug and shake hands. Massage therapy reduces pain and stress and can provide benefits for patients with psychiatric disorders.”

“In these experiments with mice, we have identified a key neuropeptide and a hard-wired neural pathway dedicated to this sensation.”

Our sense of touch is academically divided into two parts: discriminative touch, and affective touch. The first is the sense that allows us to determine that something is coming into contact with our bodies, the force with which it does so, and the exact location where it is happening. The second — which can be ‘pleasant’ or ‘aversive’ — also includes a strong emotional value to the sensation of touch.

While studying affective touch in humans is easy, as participants can report on the sensation, doing the same with lab animals is exceedingly difficult. Researchers can only indirectly infer the emotional response of an animal to a particular touch, by observing their behavior.

In order to determine this, Chen’s team placed their lab mice in single-mouse cages, apart from the rest of the mouse community (these animals are usually kept in large groups, as they are quite social). The lack of physical interaction made the mice more willing to be stroked with a soft brush by the researchers, which produces a sensation similar to petting or grooming.

After several days of brushing, the mice were placed into an experimental environment where they could choose to go in one of two chambers. In one, they would be brushed; in the other, no extra stimulus of any kind would be delivered. The mice chose the brushing chamber virtually every time. This step established that the mice enjoyed the sensation and would seek it out (heavily suggesting that it was pleasant for them).

Next, the team worked to identify potential neuropeptide candidates for the mediation of this pleasant touch sensation produced by brushing. The search led them to the prokinecticin 2 (PROK2) molecule in sensory neurons and the prokineticin receptor 2 (PROKR2) molecule in the spinal cord, which ferried this sensation to the brain. When breeding mice genetically-engineered to lack PROK2, the team found that these animals could not sense pleasant touch, but continued to respond normally to other touch stimuli such as itchiness. Mice engineered to lack PROKR2 in their spinal cords also avoided activities such as grooming and showed signs of stress not seen in control mice.

Further experiments confirmed that the PROK2 pathway is a dedicated pathway for pleasant touch and does not transmit other types of physical stimuli.

“This is important because 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 explained.

Mice who lacked the ability to sense pleasant touch from birth had more severe responses to stress and showed much more social avoidance behaviors than mice whose sense of pleasant touch was blocked when they were adults. This, Chen says, highlights how important maternal touch is for the healthy development of offspring.

“Mothers like to lick their pups, and adult mice also groom each other frequently, for good reasons, such as helping emotional bonding, sleep and stress relief,” he said. “But these mice avoid it. Even when their cagemates try to groom them, they pull away. They don’t groom other mice either. They are withdrawn and isolated.”

The paper “Molecular and neural basis of pleasant touch sensation” has been published in the journal Science.