When a person’s feelings are hurt, the pain is real. University of California, Los Angeles psychologists have determined for the first time that a gene linked with physical pain sensitivity is associated with social pain sensitivity.

Their study indicates that variation in the mu-opioid receptor gene, often associated with physical pain, is related to how much social pain a person feels in response to social rejection. People with a rare form of the gene are more sensitive to rejection and experience more brain evidence of distress in response to rejection than those with the more common form.

In the study, researchers collected saliva samples from 122 participants to assess which form of the OPRM1 gene they had and then measured sensitivity to rejection in two ways. First, participants completed a survey that measured their self-reported sensitivity to rejection. They were asked, for example, how much they agreed or disagreed with such statements as, “I am very sensitive to any signs that a person might not want to talk to me.”

Next, a subset of this group, 31 participants, was studied using functional magnetic resonance imaging during a virtual ball-tossing game in which participants were ultimately socially excluded. Subjects were told they would be connected via the Internet with two other players who were also in imaging scanners, and that they would all be playing the interactive ball-tossing game. In reality, however, participants were playing with a preset computer program, not other people.

Initially, participants were included in the activity but were then excluded when the two other “players” stopped throwing the ball to them.

“What we found is that individuals with the rare form of the OPRM1 gene, who were shown in previous work to be more sensitive to physical pain, also reported higher levels of rejection sensitivity and showed greater activity in social pain–related regions of the brain—the dorsal anterior cingulate cortex and anterior insula—in response to being excluded,” study co-author Naomi Eisenberger said.

“Because social connection is so important, feeling literally hurt by not having social connections may be an adaptive way to make sure we keep them,” Eisenberger said. “Over the course of evolution, the social attachment system, which ensures social connection, may have actually borrowed some of the mechanisms of the pain system to maintain social connections.”

The research was published in Proceedings of the National Academy of Sciences.