Monday, June 06, 2016

Advil Increases Social Pain (if you're male)

A recent neuroessay in the New York Times asked, Can Tylenol Help Heal a Broken Heart?
What’s crazy about the pain of a broken heart is that your body perceives it as physical pain.
No it does not. Do you feel heartbroken every time you stub your toe?

Well... I guess the social pain = physical pain isomorphism is a one way street. Anyway, the author continued:
In research published in 2010, scientists found that acetaminophen can reduce physical and neural responses associated with the pain of social rejection, whether in romantic relationships, friendships or otherwise.
The pain reliever Tylenol (acetaminophen) lessens the pain of social rejection, according to the 2010 study in Psychological Science [except when it doesn't].1 Acetaminophen also purportedly soothes the existential angst of watching a David Lynch film, blunts your emotions, and kills your empathy.2

So if you’re hurting from heartache, try popping some Tylenol.
Do not pop Tylenol after a breakup. It can cause serious liver damage if you take too much.

But What About Advil?

A 2014 study in the journal Personal Relationships was the first to break the stranglehold of acetaminophen (Vangelisti et al., 2014). The paper made few headlines (an exception was the Daily Mail), and it was not cited by the Tylenol researchers after its publication. Yet I saw no difference in quality, and even found more to like about it compared to the Tylenol papers (all of which appeared in higher impact journals). One of the Advil authors was Dr. James Pennebaker, chair of Psychology at the University of Texas. Dr. Pennebaker is well-known for his research on text analysis and what word choice can reveal about sex, age, social class, personality, mood, and affective state.

The focus of the study by Dr. Anita Vangelisti and colleagues was on potential sex differences in the effects of a physical pain reliever on social pain. They cited evidence suggesting that women are more sensitive to physical pain, and men might be more responsive to pain relievers like ibuprofen (Walker & Carmody, 1998).

Proposed explanations for sex differences in pain and analgesia include the bullet list below (Mogil & Bailey, 2010). These could potentially influence the effects of ibuprofen (and acetaminophen) on social pain.3
  • Sociocultural manly and stoic machismo
  • Psychological greater negative affect and catastrophizing in women
  • Experiential women may have more experience with clinical pain, which affects current pain perception
  • Opioid receptors and especially their interactions with gonadal hormones
  • Other potential biological factors a long list

Advil Worsened Social Pain in Men

Ibuprofen did indeed increase ratings of social pain in male participants, but decreased ratings in female participants Vangelisti et al. (2014). For more details, read on.

The participants were 138 undergraduates enrolled in communication courses (62 male and 76 female). Half took 400 mg ibuprofen (the dosage in 2 tablets), and half took placebo. In one task, they rated their feelings after being excluded from a ball-tossing video game (Cyberball), similar to the 2010 study of Dewall and colleagues. In the second task, they wrote detailed descriptions about an experience of betrayal by a close relational partner and an experience of physical pain. Participants completed the Positive and Negative Affective Schedule (PANAS) before treatment and after each of the tasks. On the PANAS, respondents rated their experience of 20 different feelings or emotions on a 7-point scale (1 = very slightly or not at all, 7 = extremely).4

Two additional items assessed social pain or hurt. One required participants to rate the extent to which they felt hurt; the other required them to indicate the degree to which they felt emotionally injured. An average of these two questions comprised the dependent measure of Social Pain (presumably also on a 1 to 7 scale). Another dependent measure used the Linguistic Inquiry and Word Count (LIWC) program to calculate a weighted percentage of Emotion Words and First-Person Pronouns in the written narratives, both of which are indicators of increased social pain. Neither linguistic measure reached statistical significance, so I'll focus on Social Pain ratings.

Within-subjects comparisons showed that in all cases, Social Pain ratings were higher after the tasks than before.

Placebo Group
Before        M = 1.52, SD = 0.86
Cyberball     M = 2.07, SD = 1.31
Betrayal      M = 3.12, SD = 1.62

Treatment Group
Before        M = 1.54, SD = 1.01
Cyberball     M = 1.93, SD = 1.11
Betrayal      M = 3.04, SD = 1.71

Pre-treatment ratings didn't differ between men and women, but post-treatment Cyberball and Betrayal ratings showed crossover interactions, meaning the effects were opposite in men and women. On placebo, women had higher social pain ratings than men. On Advil, women's ratings dropped but men's increased. Since women are generally lighter than men, these analyses controlled for weight effects on dosage, since everyone got 400 mg.

- click on image for a larger view - 

So the women responded in the predicted way, based on past research. But the men did not. Did the subjects' expectations influence the results? The study description specifically stated it “was being conducted to examine the link between physical and emotional pain.” In contrast, the Tylenol studies were a little more vague: “advertised as a general assessment of the cognitive and emotional impacts of acetaminophen” for the study of existential angst, and “Tylenol and social cognition” for the blunted emotion experiment.

The authors proposed a social cognitive model:
Because men are comparatively likely to curb their emotional pain, it is possible that men who take a physical pain reliever will display a disinhibition effect. That is, when men take a physical pain reliever, their cognitive response may act to blunt or inhibit their tendency to suppress their emotional pain. The cognitive processes underlying such a disinhibition effect are akin to [a] reverse placebo effect.

This didn't make sense to me, but then I found a paper that manipulated expectancy for physical pain relief in a within-subject design (Butcher & Carmody, 2012). The sample size was small (10 men, 10 women), but the participants came in once a week for 4 weeks to experience all of these conditions:
  1. Subjects told they were receiving ibuprofen and received ibuprofen (positive expectancy).
  2. Subjects told they were receiving ibuprofen but received placebo (positive expectancy).
  3. Subjects told they were receiving placebo but received ibuprofen (negative expectancy).
  4. Subjects told they were receiving placebo and received placebo (negative expectancy).
The subjects were exposed to experimentally-induced pain (electrical stimulation of the earlobe) and assessed for analgesia response (change in pain tolerance). Ibuprofen dose was 800 mg (4 tablets).

Pain tolerance in women did not differ for any of the four conditions. But pain tolerance in men conformed to their positive expectations: pain tolerance increased in both the ibuprofen and the placebo conditions when told they would receive ibuprofen. There was also negative placebo effect (a true negative placebo effect), but this was not statistically significant.

What does this mean for social pain? Although the Butcher and Carmody (2012) findings need replication, Vangelisti et al.'s disinhibition model seems to be based on expectation, not on a direct relationship between physical and social pain.

Other quibbles include the between-subjects design and small or marginal effects for some of the statistical comparisons — both of which are true for the Psych Sci Tylenol studies with their overblown interpretations. For instance, one headline from APS had this fun cure: Experiencing Existential Dread? Tylenol May Do the Trick.

To their credit, Vangelisti et al. didn't oversell their results.5 An article in The Alcade, the University of Texas alumni magazine, asked the same question as the NY Times neuroessay Can Ibuprofen Mend a Broken Heart? but arrived at a more prudent answer.
So does that mean we should all start popping ibuprofen whenever our feelings are hurt? Absolutely not, says Vangelisti. “In time, we may see psychiatrists prescribing painkillers for social pain—judiciously, I hope—but right now there are too many unanswered questions that our study has raised for this to be considered a viable treatment.”

I'll leave you with this quote from Woo et al. (2014), who found that representations of physical and social pain are clearly separable in the brain.
[Our] findings demonstrate that separate representations underlie pain and rejection despite common fMRI activity at the gross anatomical level. Rather than co-opting pain circuitry, rejection involves distinct affective representations in humans.

Thanks to @thebyrdlab for linking to the Advil paper.


1 In the Cyberball fMRI study of Experiment 2 (Dewall et al., 2010), the participants on placebo vs. those on drug did not differ in their social distress ratings after being excluded from the game.

2 Not surprisingly, I disagree with all of these overblown interpretations. See Acetaminophen Probably Isn't an "Empathy Killer".

3 By and large, social psychology researchers don't seem particularly concerned about the mechanisms of action of these drugs. I haven't written about ibuprofen, but see Does Tylenol Exert its Analgesic Effects via the Spinal Cord?

4 I thought the PANAS was on a 5-point scale, but the paper said 7-point.

5 On the other hand, we have this unfortunate statement:
"It's possible that taking physical pain relievers provides men with more cognitive resources to express the pain they feel," said Vangelisti. "There's some evidence that, for men, the part of the brain that enables them to regulate their emotions is linked to the part of the brain that processes physical and social pain. If that's the case, taking a physical pain reliever may affect men's ability to hide or suppress their social pain." 


Butcher, B., & Carmody, J. (2012). Sex differences in analgesic response to ibuprofen are influenced by expectancy: A randomized, crossover, balanced placebo-designed study. European Journal of Pain, 16 (7), 1005-1013. DOI: 10.1002/j.1532-2149.2011.00104.x

Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 21:931-7.

Mogil JS, & Bailey AL (2010). Sex and gender differences in pain and analgesia. Progress in brain research, 186, 141-57 PMID: 21094890

VANGELISTI, A., PENNEBAKER, J., BRODY, N., & GUINN, T. (2014). Reducing social pain: Sex differences in the impact of physical pain relievers. Personal Relationships, 21 (2), 349-363 DOI: 10.1111/pere.12036

Walker JS, Carmody JJ. (1998). Experimental pain in healthy human subjects: gender differences in nociception and in response to ibuprofen. Anesth Analg. 86(6):1257-62.

Woo CW, Koban L, Kross E, Lindquist MA, Banich MT, Ruzic L, Andrews-Hanna JR, & Wager TD (2014). Separate neural representations for physical pain and social rejection. Nature Communications 5: 538.

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