Taking Tylenol for Heartache: The Relationship Between Physical and Emotional Pain

Adapted excerpt from WE HAVE THE TECHNOLOGY: How Biohackers, Foodies, Physicians, and Scientists are Transforming Human Perception, Once Sense at a Time by Kara Platoni. Copyright (c) 2015. Available from Basic Books, an imprint of Perseus Books, a division of PBG Publishing, LLC, a subsidiary of Hachette Book Group, Inc.

Naomi Eisenberger's office overlooks the sprawling UCLA campus. She’s been here her entire career, starting as a graduate student in health psychology. She was intrigued right off the bat by the connection between the social and the physical— “How is it that what goes on in our heads seems to influence what goes on in our bodies? Why does stress make us sick?”— and drawn to the neuroscientific techniques that have made these connections increasingly possible to examine.

She got hooked on studying social pain from the very beginning. “I think I have just always been curious about rejection,” she says in a soft, soothing voice. “Why does it seem to affect people so much? A lot of people have memories of early childhood experiences of being picked last for teams or left out by their friends on the playground.” In her own life as a grad student, she’d noticed this fear of rejection showing up as nervousness about public speaking.

One time, when she had a quiet moment by herself before a speech, she became suddenly aware of how rapidly her heart was beating. “It really feels like I’m being held up at gunpoint,” she thought to herself, “and this is weird, because all I’m doing is giving a talk.”

Eisenberger began studying the brain activity of people who had been socially rejected as part of a lab experiment. One day as she was looking at her data, she happened to be sitting next to a friend who was analyzing data from a pain study of patients with irritable bowel syndrome. “We just sort of noticed, ‘Isn’t that weird? The activations that you are seeing in your irritable bowel syndrome patients who are being exposed to painful stimulation look really similar to what we are seeing in this rejection study,’ ” she recalls. “These two things, maybe they are more similar than we thought. Maybe it’s not just a metaphor.”

What is Pain?

Now if you want to get to the bottom of whether social rejection actually hurts, the first dumb question you have to ask is, well, what is pain? And it turns out that the answer is not so obvious. When I ask Eisenberger, there’s a long pause. “That’s a super hard question!” she finally says with a light laugh.

“And I think depending on who you are talking to, different people care about different aspects of pain.”

For the record, she points out, there is an official definition, issued in 1979 by the International Association for the Study of Pain, a group of scientists, doctors, and others who research and advocate for pain relief. Their definition is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” That’s incredibly broad; it really tells you a lot more about how pain feels (bad) than how it works. But it’s telling that it encompasses the very linguistic mystery that Eisenberger and her colleagues set out to unpack. What is a broken heart if not an emotional experience described in terms of tissue damage?

There are reasons why describing pain is so hard. For one thing, it’s difficult to objectively measure something that is inherently subjective, points out Dr. Sean Mackey, chief of the Division of Pain Medicine at Stanford University, whose lab has also researched the idea of overlap between social and physical pain. How do you turn the sensation of pain into something you can count? “There is not a direct one-to-one correspondence between a specific quantum of stimulus and experience of pain,” Mackey says. How much pain a person experiences from a given stimulus can vary greatly— what is awful for one person might be tolerable, or even barely noticeable, for the next. Without an objective way to measure how much pain a person is in, medical and mental health practitioners must rely on the same feedback mechanism: the patient's self-report.

Pain is also polysensory; we feel it through many channels. People often think of touch first when it comes to pain, and some researchers indeed classify pain as a subset of somatosensation, the larger category that includes touch and temperature. We have nociceptors, or pain sensors, throughout our skin and soft tissue that are sensitive to environmental changes that might cause us bodily damage— pressure, temperature, chemical acidity. These nociceptors let us know when we’ve pinched our fingers in a drawer or burned our tongues on hot pizza or gotten shampoo in our eyes. It’s important to note that when we experience pain this way, it’s not because we’ve overstimulated the regular touch mechanoreceptors. We’ve actually activated an entirely separate system of receptors that don’t kick on until the force, temperature, or chemical irritant we are experiencing reaches a certain dangerous level. These impulses are relayed to the brain through a pathway separate from touch.

But, Mackey argues, you can experience pain through any of your senses, not just touch. Ordinary light doesn’t hurt the eyes, but if the light’s too bright, he asks, “ doesn’t the light stimulus then become painful? And the same with sound. If you happen to have your ear next to a gunshot, isn’t that painful? You are exceeding a certain threshold for the sound pressure waves to be perceived as painful. What we believe is that these other sensory inputs can actually engage the same type of pain systems as if you hit your thumb with a hammer.”

That’s an important idea: Pain has multiple sensory pathways that all feedback to the brain. Technically, Mackey says, what happens in the body (what a neuroscientist would refer to as the periphery, made up of the nerves and the spinal cord) is not exactly pain. It’s nociception, or the translation of real-world data into electrochemical signals signaling pain. Those signals get piped to the brain, where perception truly happens. “Pain is fundamentally a brain-related phenomenon,” Mackey says. The brain is where it all registers, “where the perception of pain is processed and perceived and modulated.”

Another complication is that pain has several components, although not all researchers tally them up the same way. Eisenberger likes to speak of pain as having two main parts. The first is its sensory component, which is mainly objective information: Where is the pain coming from on the body, how intense is it, what is its nature? For example, she says, “is it a burning pain or an aching pain?” The second is its affective or emotional valence, how distressing or bothersome it is, and your urge to reduce its unpleasantness. Mackey thinks there are at least three components, possibly four. The third he calls the “cognitive evaluative” component, or your thought processes about how to get away from the pain and what the pain means. The fourth, which he says is less accepted and perhaps related to the third, is the idea of behavioral avoidance, or doing things to prevent future pain. In fact, that behavioral and motivational aspect of pain is probably the key missing component of the definition of pain, Mackey says. (Some experts combine these last three categories under a broader "affective- motivational” heading.)

Different brain areas seem to be in charge of handling these dimensions of pain. As you might expect, the somatosensory cortex, which is involved with sensing touch, is involved with sensory pain. The anterior cingulate cortex and insular cortex— involved in processing emotion— are involved with pain’s affective dimension. The prefrontal area, which is involved in planning and decision making, is linked with its cognitive aspects. But, says Mackey, there’s really no clean break between these areas, which function as part of a larger system. “All of these regions are intimately connected to each other and each one is modulating the others,” he says. Many researchers refer to this as the “pain matrix,” says Eisenberger, a distributed network of regions that activate when you feel pain. “Some are involved more in sensory components, and some are more involved in the affective experience,” she says.

Tylenol and Lost Love

And it’s here, within this idea of overlap and blur, that we get to Tylenol and lost love and fMRI scanners. If these areas are truly cross-chatting, painkillers that work to calm muscle tension should work to quell heartache, and vice versa -- love should be a balm. Or in experimental terms, says Eisenberger, “if we turn up physical pain, does that turn up social pain? If we turn down social pain, does that turn down physical pain?”

This idea has its roots in the 1970s, when neuroscientist Jaak Panksepp realized that giving infant monkeys morphine— a potent painkiller— made them produce fewer distress cries when separated from their mothers. It was an important clue that an analgesic for physical pain reduced social pain. Other research avenues have explored how psychological factors can influence physical pain perception, like how the context of pain changes how strongly you feel it. Then there’s the placebo effect: Why do people taking inactive pills report that they feel better? But Eisenberger’s group was the first to test Panksepp’s idea in humans by putting people into a scanner and, well, rejecting them.

It’s actually hard to reject someone who is lying inside a giant magnet. You can’t get anyone else in there. They’re not allowed to talk or move. It’s so noisy that they can’t really hear. But they can play Cyberball. Cyberball is the brainchild of Kipling Williams, a psychology professor at Purdue University, who came up with the idea after being slowly excluded from a real-life game of Frisbee that he’d run across in a park. In Cyberball, study subjects are asked to pass a virtual ball back and forth with several other players. At first, the other players pass the ball back. Then they start ignoring the subject, making it a game of virtual keep-away. The other “players” are actually a computer, programmed to eventually exclude the person. But the subject doesn’t know that, and feels stung by the snub.

In their first 2003 study, Eisenberger and Williams’ group found that rejecting Cyberball players caused greater activity in the dorsal anterior cingular cortex (dACC) and anterior insula (AI), both regions otherwise associated with physical pain. And over the next several years, Eisenberger’s lab explored variations on this theme. They found that people who score high on tests for sensitivity to rejection have a heightened dACC response when shown images of disapproving faces. People asked to participate in an interview and then get feedback from an “evaluator” (really, a lab researcher) while lying in the scanner showed a bounce in dACC and AI activity after hearing themselves described with words like “boring” that connote rejection, but not after hearing neutral or accepting words. Teenagers who spend more time with friends show less activity in these pain areas when rejected during Cyberball.

Other labs were exploring, too. One particularly interesting 2011 study, led by social psychologist Ethan Kross at the University of Michigan, asked people who had just been through unwanted breakups to look at pictures of their exes, arguing that this painful stimulus would be even more acute than being left out of an imaginary game or criticized by strangers. Subjects lying in the scanner either looked at a picture of their former partner and thought about being rejected by them or viewed a photo of a friend and recalled a recent positive experience with them. To establish a baseline of which brain areas react to physical pain, a separate group of subjects was scanned while feeling either painfully hot or neutrally warm stimulation on their forearms. (Pain in these experiments is typically administered to the arm using a small
wand with an electric thermode at the end that delivers a sharp heat; it feels, Eisenberger says, more like a sting than a burn.) The researchers found that not only did people report more pain when looking at their exes, but their brains showed more activity in the dACC and AI areas— the same ones that became more active for the people touching the hot object.

With the evidence mounting that social pain inflames the brain’s physical pain centers, it was time to try the reverse: to see if you could use physical pain remedies to calm social pain down. In 2010, social psychologist Dr. C. Nathan DeWall at the University of Kentucky, collaborating with Eisenberger and others, tested the social pain-killing power of Tylenol, or rather, the generic acetaminophen. DeWall first asked his subjects to take either acetaminophen or placebo pills daily. Every night, they logged how much social pain they had experienced that day using a “Hurt Feelings Scale” developed to gauge the pain of rejection, but not other negative emotions. They also recorded their day using a separate scale that measured positive feelings. After three weeks, the subjects taking the acetaminophen reported fewer hurt feelings than those on the placebo, but not an increase in good ones, suggesting that the drug was tamping down bad feelings, not enhancing the positive ones.

In the next stage of the study, DeWall’s subjects once again took either acetaminophen or a placebo for three weeks, and then got in the scanner to play Cyberball and be roundly rejected. The participants who took the acetaminophen showed less activation in both the dACC and the bilateral anterior insula. (Interestingly, while their brain activity differed, being left out of Cyberball felt equally distressing to both groups.) These results, DeWall says, suggest that “we put all of these different painful or unpleasant events in separate buckets in our heads, but there is a common mechanism underlying them.”

So should doctors start prescribing Tylenol for people going through breakups? “I don’t know,” DeWall muses. While the authors didn’t go so far as to recommend that people start routinely popping Tylenol to inure themselves to negative feelings, they did write that it might offer temporary relief from social pain, and suggested further research to see if it can also dampen the aggression and antisocial behavior that can follow rejection. Since the study came out, DeWall says, he’s gotten a lot of letters from people sharing anecdotes about their own attempts to self- medicate for a broken heart, but so far there’s been no clinical trial testing Tylenol on the lovelorn.

There’s an X factor, too, in that it’s not very well understood how acetaminophen kills pain in the first place. “Does it work on central pain versus peripheral pain?” asks DeWall. “Honestly, we don’t know enough to make a definitive statement about it.” But he does know that it activates cannabinoid1 brain receptors, which are also activated by THC, the psychoactive component of marijuana. In 2013, along with several collaborators, he published the results of four studies investigating the effect of pot on social pain. The first three were correlational analyses, in which they argued that marijuana use correlates with lower self-reports of loneliness and incidents of serious depression, both indicators of social alienation. The fourth asked people to play Cyberball, but only half of them got a version in which other players excluded them. Afterward, the players filled out a scale that assessed how threatened they felt their emotional needs— self-esteem, belonging, control— were during the game. Frequent marijuana smokers reported feeling less threatened than the infrequent ones. Again, the authors didn’t suggest everyone light up to avoid social pain—in fact, they wrote, people might smoke pot because they feel socially rejected. But they did suggest that both drugs suppress social pain by acting on the same cannabinoid 1 receptors, and pointed out that once again a drug that is—at least in some states— legally used for physical pain seems to also alleviate social distress.