Social beasts—humans, elephants, chimps, dogs, and cats—seem to enjoy being caressed. Neurobiologists have now taken a step toward pinpointing neural circuitry underlying this pleasant sensation. Using genetically engineered mice, they demonstrated that a specific class of sensory cells in skin reacts to gentle stroking but not to a pinch or a poke. In addition to helping to identify similar cells in people, the findings could "lead to a drug or lotion that might make you feel better," suggests study leader David Anderson, a neurobiologist at the California Institute of Technology in Pasadena.
The skin is full of nerve endings that respond to mechanical stimuli—often registering pain. In social animals, grooming is a key component in building and maintaining good relationships. Thus, it makes sense that specialized nerve cells evolved to relay a pleasant sensation when activated.
Anderson and his colleagues didn't set out to explain the pleasure caused by caressing. Instead, they were seeking to understand a type of sensory cell that they discovered in mice in 2007.They were present only in hairy skin, with a very spread out distribution of nerve endings. "We thought these must be very specialized neurons that detect a very specialized type of stimulus," Anderson recalls. But the typical tests in isolated patches of skin to determine what the neurons were sensitive to didn't work. "We had to figure out a way to determine what turns these neurons on in a living intact animal," he says. "That has never been done before."
The researchers inserted a gene into mouse embryos that would make these neurons light up when activated. They watched for this activity by opening a small hole along the spine of the mouse through which a microscope could detect when the nerve cells lit up. They tried various types of stimuli to see if they could get the cells to light up. For example, the scientists recorded each time they stroked the hindfoot of the mouse with an artist's paintbrush. In this way, they could see if the touch was responsible for the nerve signal. Gentle stroking, but not poking or pinching with a tweezer, elicited a response, Anderson and his colleagues report online today in Nature.
But does such a soft touch feel good? To find out, the team genetically modified other mice so that these touch-sensitive neurons could be activated with a drug injection. The scientists then tested whether the mice would come to prefer being in a place where drug-induced "touching" occurred. They built a three-chambered box with doors connecting each end chamber to a middle one. Each end chamber had a distinctive feel, smell, and color scheme so the mice could tell the difference. The researchers first noted which end chamber each mouse favored. Then they put the drug-injected mice in the other end chamber for two hourlong sessions. On alternate days, they injected the mice with a salt solution that had no effect on the nerves and put them in the "preferred" end chamber for an hour at a time.
At the end of this conditioning regimen, they put the mice in the middle chamber and let them choose where to go. In contrast to pretest preferences, the mice spent most of their time in the chamber where they were given the drug. "It implied the treatment was rewarding and certainly not negative," Anderson says. The assumption is that this positive reinforcement reflected a calming effect on the mice.
Researchers had detected gentle moving sensitive nerves before but had not pinned down the molecular identity of those nerves. Nor had anyone linked that sensitivity back to behavior. "That's what [Anderson and colleagues] have accomplished," says India Morrison, a neuroscientist at the University of Gothenburg in Sweden. The findings "imply that social touch is not simply nice, but that it has calming power in the context of something less-than-wonderful."