Acetaminophen May Also Relieve Psychological Pain

Janis C. Kelly

December 30, 2009

December 30, 2009 — Opiates and other strong analgesics have long been known to numb psychological as well as physical pain, but new evidence suggests that even mild over-the-counter drugs like acetaminophen may relieve psychological discomfort, such as the stress of social rejection.

A research team led by psychologist C. Nathan DeWall, PhD, from the University of Kentucky College of Arts and Sciences, Department of Psychology, Lexington, examined the overlap between neural and psychological pain by randomly assigning healthy volunteers to 3 weeks of either daily acetaminophen or placebo, then comparing self-reports of social pain.

In a second study, the researchers used functional magnetic resonance imaging in an attempt to correlate changes in brain activity in regions believed to be associated with responses to social rejection with subjects' experiences of social pain.

"The idea that a drug designed to alleviate physical pain should reduce the pain of social rejection seemed simple and straightforward based on what we know about neural overlap between social and physical pain systems. To my surprise, I couldn't find anyone who had ever tested this idea," Dr. DeWall said.

He described "social pain" as "a painful affective response to a perceived threat to social belonging. Social rejection is one example of a socially painful event."

The research is due to be published in an upcoming edition of Psychological Science.

Hurt Feelings Measured

The first experiment included 62 healthy volunteers randomly assigned to 1000 mg/day of either acetaminophen or placebo. Each evening, participants used a version of the Hurt Feelings Scale to report how much social pain they experienced that day.

As expected, hurt feelings decreased significantly over time among participants who took acetaminophen (P < .05), but they were unchanged in the placebo group, the researchers report.

"These data provide some of the first evidence that reducing physical pain can reduce the pain of social rejection. They add to our understanding of how seemingly different types of painful experiences are processed through the same neurobiological systems," Dr. DeWall told Medscape Psychiatry.

In the second experiment, the acetaminophen dose was doubled to 2000 mg/day in an attempt to compensate for the lower statistical power associated with the smaller groups (10 participants randomly assigned to acetaminophen, 15 participants randomly assigned to placebo).

After 3 weeks of taking the pills, the subjects participated in a computer game rigged to create feelings of social rejection.

Functional magnetic resonance imaging findings showed that the acetaminophen group had significantly less neural activity than the placebo group during the game in brain regions associated with the distress of social pain and with the affective component of physical pain (the dorsal anterior cingulate cortex and anterior insula).

However, the acetaminophen and control groups "reported equal levels of social distress in response to the exclusion episode," the researchers report.

Potential to Reduce Violent Behavior?

Dr. DeWall said that despite the drug's lack of effect on the experience of social distress, the researchers concluded that acetaminophen reduced the pain of social rejection at the neural level.

The data "suggest that at least temporary mitigation of social pain–related distress may be achieved by means of an over-the-counter painkiller that is normally used for physical aches and pains."

The investigators further suggest that acetaminophen may prevent violent behavior, as "many studies have shown that being rejected can trigger aggressive and antisocial behavior, which could lead to further complications in social life.... If acetaminophen reduces the distress of rejection, the antisocial behavioral consequences of rejection may be reduced as well."

"This research has the potential to change how scientists and laypersons understand physical and social pain. Social pain, such as chronic loneliness, damages health as much as smoking and obesity. We hope our findings can pave the way for interventions designed to reduce the pain of social rejection," said Dr. DeWall.


Asked by Medscape Psychiatry to comment on the study, Bruce G. Charlton, MD, applauded the investigators' research efforts.

"It is particularly difficult to get research funding to study old, cheap, unpatented, over-the-counter drugs, so I congratulate the authors on doing this," he said.

Dr. Charlton, who is editor-in-chief of Medical Hypotheses and professor of theoretical medicine at the University of Buckingham, United Kingdom, agreed that different sorts of pain are often related, so there is good reason to assume that acetaminophen or paracetamol may benefit those who suffer any type of pain of unpleasant feelings, including some types of depression.

However, he noted that the same effect would likely apply to aspirin, nonsteroidal anti-inflammatory drugs, and opiates, "about which there is more evidence," he said.

Alternative Interpretation

Magne Arve Flaten, MD, from the department of clinical research at University Hospital of North Norway, Tromso, also commented on the study for Medscape Psychiatry. Dr. Flaten, who recently published a study of cognitive and emotional factors in placebo analgesia, said that alternative interpretations of the data are possible.

"The authors seem to think that rejection induces 'social pain,' but it would probably, in my view, be more correct to say that both pain and social rejection are associated with unpleasantness and other negative emotions.

"Social pain is not pain as we ordinarily think of it, but it shares some of the emotional aspects that pain has, and aspects that probably other negative emotions also have," said Dr. Flaten.

He noted that the investigators' first experiment showed that acetaminophen reduced "hurt feelings," but that the effects, although significant, "seem small." He suspects that the researchers' inability to replicate the psychological effect in the second experiment may have been a result of lack of power because of the small sample size.

"I do not think this research tells us anything about pain, since pain, in a normal sense of the word, was not investigated in these experiments. The research tells us that acetaminophen could reduce some of the negative emotional consequences of social rejection, which is very interesting," Dr. Flaten said.

The study was funded by the National Institute of Mental Health and the Gulf Atlantic Group Incorporated. Dr. DeWall, Dr. Flaten, and Dr. Charlton have disclosed no relevant financial relationships.

Psychol Sci (in press).


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