The Nuance

The Fascinating Brain-Pain Connection

How expectation, emotion, and other neurocognitive factors affect our perception of pain

Illustration: Kieran Blakey for Elemental

Imagine that you’re about to have a tooth pulled. Your dentist tells you that, unfortunately, the tooth’s roots are infected, and so the procedure is going to hurt. A lot. It can’t be helped.

Now imagine an alternate scenario. You still need that tooth pulled, but this time your dentist says nothing — one way or the other — about the pain you may feel.

In both of these scenarios, the painful stimulus is the same. The same tooth is going to be pulled, and it will probably hurt either way. But would you experience the same amount of pain? Almost certainly not. Your dentist’s comments — not to mention your mood, stress levels, and other factors — are capable of shifting your perception of pain in one direction or the other.

“What we experience — second to second, moment to moment — is an interaction of what’s coming in from the outside but also top-down processes from the cortex of the brain,” says Irving Kirsch, PhD, director of the Program in Placebo Studies at Harvard Medical School and Beth Israel Deaconess Medical Center.

Kirsch has spent much of his career examining the variables that affect these top-down processes. He explains that the amount of pain you feel will always be influenced by expectation — for example, if a dentist tells you something is about to hurt — as well as by emotion, attention, motivation, and other factors. This influence can be subtle or significant, but it’s never absent.

“We used to have this view of pain or other sensory processes as being some sort of veridical picture of objective reality, but we’ve learned that that’s not how perception works,” says Tor Wager, PhD, a distinguished professor in neuroscience at Dartmouth College. “We get signals from our body, but they’re not the only source of information that our brain uses to construct what we perceive.”

These and other new insights into the brain’s role in pain could transform the way doctors approach its management. These findings also have broader implications for the brain and its relationship to consciousness, reality, and all forms of human experience — good or bad.

The brain’s role in acute and chronic pain

Of all the top-down factors that influence a person’s experience of pain, Wager says that attention is probably the most impactful. “The more we pay attention to something, the more its signal is amplified,” he says.

To illustrate his point, he describes a person being chased by a charging rhinoceros. “If that person steps on a thorn, they’re not going to experience much pain in that moment,” Wager says. That person’s attention is so fully captured by the rhino that it doesn’t have any left for the painful thorn. In this situation, the brain’s perception of pain is turned down almost to zero.

Unpleasant experiences of all kinds are not distinct phenomena in the brain; they appear to blend together and feed one another like the tributaries of a river.

Wager says that expectation and past experience are both powerful magnets for our attention. If you feel like something is going to hurt, your brain is going to be on the lookout for pain, which will turn up its volume.

For a 2017 study in the journal Emotion, Wager and his colleagues found that social influence also has an effect on felt pain. When people in the study learned that others in their position had rated an experience as painful, their own experiences tended to swing heavily in that direction. Wager says that, in some cases, this swing is actually visible. “We can see that the area of the brain that encodes a painful experience — and all its surrounding feelings and experiences — is altered,” he says.

This “all its surrounding feelings and experiences” alteration is a big deal. More of Wager’s brain-imaging work has found that social rejection shares a lot of activity with physical pain. Research has also found that sadness, worry, and other negative emotions exacerbate physical pain. All of this suggests that unpleasant experiences of all kinds are not distinct phenomena in the brain; they appear to blend together and feed one another like the tributaries of a river.

Wager says that all of these interrelated, top-down factors usually account for just a fraction of the pain we feel — probably something on the order of one-third of our perception of pain. The other two-thirds typically come from pain signals that our body sends up to the brain. “We are capable of hallucinating — our brain can create something that isn’t there — but that’s not how we normally operate,” he says.

However, the experience of chronic pain may play by different rules.

According to a recent report from the CDC, roughly one in five adults experiences chronic pain — defined as pain that occurs most days or every day for a period of at least three months. Back pain is the most common — and therefore the most studied — of these chronic conditions. And there’s evidence that, over time, this pain may become decoupled from any lingering injury.

For a 2013 study in the journal Brain, researchers compared brain-imaging data collected from people with either new or chronic back pain. Among the people with new back pain, the images revealed nothing out of the ordinary; brain activity was mostly limited to areas that tend to fire up during all kinds of painful experiences. But for those with chronic pain, the images revealed very little of this acute-pain activity. Instead, emotion-related circuitry was heavily involved.

“Back pain that persists for more than a few weeks has a 50/50 chance of becoming chronic — which is a huge number — and what determines a person’s risk is brain anatomy and physiology, not the initial injury,” says Apkar Apkarian, PhD, one of the authors of the study and director of the Center for Translational Pain Research at Northwestern University.

Apkarian has been studying pain for decades, and his work is at the forefront of the field. He says that, without a doubt, some brains have functional and structural properties that predispose them to chronic pain. While not all pain conditions are the same, he says that the experience of chronic pain is often dominated by top-down processes, rather than from pain signals emanating from an injury site. “Even in arthritis, where we think of irritation from degenerated joints as driving pain perceptions — even in those cases, we see a lot of brain involvement,” he says.

Exactly what makes some brains vulnerable to chronic pain is an open question. Apkarian says it’s probably a combination of genetics and experience, rather than one or the other. But it’s clear that chronic pain is more closely tied to learning processes in the brain than it is to any ongoing insult or injury.

“There is no such thing as a fake perception. Everything you perceive is always a creation of your brain.”

A lot of questions remain unanswered. But Apkarian says he’s hopeful that his and others’ work will soon produce better forms of treatment for chronic pain — including more effective drugs. “We know that treating chronic pain with opioids is definitely the wrong thing to do,” he says. Not only are these drugs perilously addictive, but they also target receptors in the brain that don’t seem to be heavily involved in chronic pain. “We’re looking at some potential drug therapies that act on the brain and that do not involve the opioid circuits,” he says.

“Right now, there are also alternative treatment options that seem to work much better than opioids,” Apkarian says. These include mindfulness meditation, yoga, and other options that seem to work in part by targeting the brain, rather than the site of a person’s pain.

Clearing up a big misconception

Some may regard pain that is generated in the brain as somehow fake or imagined. But experts say this is nonsensical. “There is no such thing as a fake perception,” Apkarian says. “Everything you perceive is always a creation of your brain.”

Wager makes a similar point. “What you perceive is always a gestalt — it’s a model or a simulation of the world that your brain creates,” he says.

The brain is always filtering and interpreting — always attending to a narrow slit of incoming information while ignoring everything else, he says. And so what we experience — pain or pleasure, joy or sorrow — is always a cocktail of objective and subjective ingredients.

“This is really a radically different view of how perception and consciousness work,” Apkarian says. “But this is what the evidence we have points to.”

I write about health and science. I live in Detroit with my wife and kids. I’m trying to learn German, but my progress so far is nicht gut.

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