A team of researchers that includes three current and former Foundation-funded scientists has discovered that the same brain system known to ease sustained physical pain may also ease pain when people are rejected in social situations. It’s the first time that opioids―naturally occurring painkillers active in the brain and other parts of the body―have been observed to be released in the brain during social rejection, and may have a protective effect. It has been known for over 30 years that opioids are involved in social distress in animals.

“Our team’s work shows that responses to social rejection and physical pain share similar neurochemical pathways,” said the researchers, who included David T. Hsu, Ph.D., a 2011 NARSAD Young Investigator Grantee, lead author on a paper reporting the finding published August 20th in Molecular Psychiatry. Other authors included three-time NARSAD Grantee Jon-Kar Zubieta, M.D., Ph.D., and 2007 NARSAD Young Investigator Grantee, Scott A. Langenecker, Ph.D. Drs. Hsu and Zubieta are based at the University of Michigan, and Langenecker at the University of Illinois in Chicago.

“Although much research has yet to be done, the results point to a potential mechanism underlying sensitivity to negative social evaluation, seen in some forms of major depression and bipolar disorder, social anxiety, eating disorders, and borderline personality disorder,” the authors said.

The team tested a group of 18 healthy volunteers aged 18-48. They were asked to select, from several hundreds of profiles, people with whom they would be most interested in forming an intimate relationship. A combination of PET (positron emission tomography) brain scans and questionnaires measured the subjects’ reactions when they received either positive or negative feedback.

Social rejection was found to increase release of the body’s natural opioids interacting with a system of cellular receptors, called the “mu”-opioid (μ-opioid) receptor. This system was marked with radioactive tracers so that changes could be noted in whether the receptor was “available” or “occupied” by the body’s own opioids when the brain scans were given.

When people were rejected, fewer receptors were available for the radioactive tracer, meaning more receptors were occupied by the body’s own opioid molecules. The inference is that the body’s opioids are released to lessen the pain of social rejection, much as they do during physical injury. This is an adaptive response, meaning that it may contribute to our ability to heal emotionally after a negative social experience.

Interestingly, people who scored higher for the personality trait “resilience,” as measured by a questionnaire before the scan, had more opioid release during social rejection in the amygdala, a structure important in emotion regulation. This suggests that more resilient individuals are more effective at delivering natural painkillers to the amygdala during social rejection.

The study also showed that being socially accepted was associated with opioid release in certain brain areas, in line with animal studies showing that the opioid system is involved in both social distress and social reward.

This work was supported in part by a NARSAD Young Investigator Grant to lead investigator Dr. Hsu to support the PET opioid research, and to Dr. Langenecker to support subject recruitment and characterization.

Read the press release from the University of Michigan.

Read the study abstract.