Pain is often thought of as a physical sensation, but it’s much more than that. It also serves as a teaching tool, motivating us to escape harm and avoid future threats.
One way it does so is by stirring up negative emotions—what researchers call the affective components of pain. But we learn not only when we experience pain ourselves, but when we see others in pain, thanks to our sense of empathy, which is our ability to understand and share someone else’s feelings.
New animal research now shows that a brain region called the anterior cingulate cortex (ACC) contains nerve cells, dubbed “mirror neurons,” that become active both when a rat undergoes pain itself and when it sees another rat experiencing pain. This work furthers our understanding of what happens in the nervous system during instances of empathy, at least in rats, but also has treatment implications for people with pain too.
“The science is very elegant,” said Luana Colloca, a pain researcher at the University of Maryland, Baltimore, US, who was not involved in the new study. Most exciting, she said, is that the researchers “identify a subpopulation of neurons that respond to shared pain, when it’s observed in another.”
The new findings come from Christian Keysers and colleagues at the Netherlands Institute for Neuroscience in Amsterdam, and appeared April 22, 2019, in the journal Current Biology. Maria Carillo and Yinging Han, also of the Netherlands Institute for Neuroscience, were co-first authors of the study.
Mirror in the brain
Mirror neurons were first identified in the 1990s, when researchers recorded the electrical activity of neurons in the motor system (the parts of the brain and body that generate movement) of a monkey as it observed a researcher picking up an apple from a table.
“These neurons activate both when you do something, and when you watch someone else do it,” Keysers said.
That discovery changed the way neuroscientists conceived of how the brain processes the actions of others, Keysers said.
“At that point, people still thought that observing other people would primarily activate visual-spatial processing in the brain. There was a belief that somehow we just make sense of it like a game of chess, in an intellectual way.” The existence of mirror neurons “was the first evidence that we don’t just engage visual and intellectual brain regions, but also those associated with our own body and actions,” he said.
Keysers and his team were interested to learn if there were mirror neurons for pain too—nerve cells that would respond both to one’s own experience of pain and when observing someone else in pain.
Looking to the ACC
The group focused its attention on the anterior cingulate cortex (ACC), a fold of brain tissue tucked in towards the center of the brain. This structure has come to be known as a hotbed of emotional processing, including the affective components of pain.
To find mirror neurons, the researchers implanted rats with electrodes to record the electrical activity of neurons in the ACC while the animals underwent pain or observed another rat in pain. Pain in the former condition was evoked by a carbon dioxide gas laser, while in the observed pain condition, rats saw another rat undergoing painful footshocks.
To qualify as pain mirror neurons, the cells needed to be selective for pain. That is, they should only respond to pain, and not other attention-grabbing, negative emotions such as fear. To prove this, the researchers exposed the rats to painful footshocks as the animals heard a 20-second tone. Later, the tone alone would evoke fear behaviors in the rats. With this experimental set-up, the researchers would now be able to compare how the neurons responded to pain vs. fear.
By recording the activity of thousands of nearby neurons, the researchers found that of the hundreds of recordings they made, about three quarters showed that neurons were responding to at least one of the conditions: pain in the self, observed pain, or fear evoked by the tone.
When the authors looked at the activity of individual cells, they found seventy-three neurons that responded to at least one of the conditions. Of those responders, 81 percent responded to observation of pain in another rat, and two thirds of those also responded to a self experience of pain or fear, qualifying them as potential mirror neurons.
“Here we observed 60 percent of the neurons that responded to pain experience [of the self] also responded to pain of the other,” Keysers said. “That was really a strikingly high number, and that shows how prevalent the representation of another animal’s pain is in a system we associate mainly with personal pain.”
“It’s been shown in humans that there is a similar, shared mechanism for ‘self’ pain and our ability to ‘feel’ the pain of others,” said Colloca. But although results from functional magnetic resonance imaging (fMRI, a type of brain scan) suggest that the same brain regions are activated by direct and vicarious pain, the technique cannot show that the same neurons are activated by the two phenomena. “This is really the first time we see direct and observed pain represented in individual neurons in an animal study,” Colloca said.
“Before this, there was no evidence for single neurons that map others’ pain onto your pain,” Keysers added.
The ability of humans to learn from one another is critical to our survival. And the finding of the mirror neurons in rats, Colloca said, “suggests it’s a very old mechanism of learning. No matter what species, animals observe one another, and experience a great learning opportunity to optimize behaviors.” That learning, she added, is an extremely complex phenomenon that occurs across multiple brain regions and involves many different types of mechanisms.
The new work also shows that those learning opportunities extend beyond simple behaviors.
“When we observe something more complex, something more emotionally associated, that can help us make inferences about the thoughts and actions of others,” Colloca said.
She also says the new findings might even translate to better pain treatments.
“They complement very well what we’re learning about social modification of pain in people, and the implications are significant,” she said. “Once we learn the mechanisms behind social learning, we can actually use that to improve therapeutic benefits.”
For example, patients might watch a video of another person undergoing successful treatment for pain. “If they can be exposed to the experience of others and learn from it, that’s much more effective than merely telling a patient, ‘we observed this benefit.’ This can amplify our ability to manage pain.”
This story first appeared on the Pain Research Forum and has been adapted for RELIEF.
Stephani Sutherland, PhD, is a neuroscientist and freelance journalist in Southern California. Follow her on Twitter @SutherlandPhD