The mu-opioid system: the brain’s natural painkillers

The mu-opioid system: the brain’s natural painkillers

Tina Pentland: News Editor

Could the brain’s natural pain relievers, the opioids, offer a new way of treating depression and anxiety? The results of a recent study carried out at the University of Michigan Medical School suggest this is a real possibility. The study, “Response of the μ-opioid system to social rejection and acceptance”, published in the Journal Molecular Psychiatry, tested the hypothesis that pain-relieving chemicals in the brain, which are activated in response to physical pain, might also respond to social pain. The focus of the study was the mu-opioid receptor system, specifically, the role of the mu receptor in regulating pain—not just physical pain, but the pain brought on by social distress (e.g., rejection).

The mu [μ] is one of three major receptors involved in the transmission and modulation of the opioids, an endogenous (or innate) system that alleviates physical pain in both humans and animals. While the opioids are known to also regulate social distress and reward in animal models it is not known if they play a part in regulating social pain in humans. However, the findings of this new study appear to confirm the initial hypothesis that the endogenous opioid system does indeed function to regulate social distress in humans, as predicted. It is with some justification, therefore, that David T. Hsu, the lead author of this new study, claims, “This is the first study to peer into the human brain to show that the opioid system is activated during social rejection.”

iStock_000009235393XSmallPeople cope with pain and rejection in different ways—being more or less able to manage pain (physical or social), and more or less resilient in withstanding pain, especially the pain of rejection and consequent blows to self-esteem. In this study, the research team at the U Michigan Molecular and Behavioural Neuroscience Institute developed an innovative methodology to test the brain’s response to social pain by combining advanced brain scanning techniques (positron emission tomography, or PET) with an online dating model that incorporated scenarios of acceptance and rejection by strangers. Participants were asked to select people they might be interested in romantically from a wide selection of photographs, just like online dating—but then they were told these people were not interested in them! Brain activity at the moment of rejection was measured in the PET scanner and the results showed that the brain areas most active at this point in time were the same areas involved in physical pain. The personality of the participants was an additional significant variable—for example, people who scored high for the resiliency trait on a personality questionnaire tended to be capable of more opioid release during social rejection, especially in the amygdala, a region of the brain involved in emotional processing.

The importance of these findings are not merely observational; rather, they open up new lines of research in treating anxiety and depression, such as developing non-addictive medications. As Hsu noted, “Increasing evidence for the neural overlap of physical and social pain suggests a significant opportunity to bridge research in the treatment of chronic pain with the treatment of psychiatric disorders.”


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