It’s not uncommon for caregivers or loved ones of chronic pain patients to also report experiencing more pain themselves. In people, it’s thought that this effect may be caused by direct social interactions that drive empathy for the patient in pain.
Now, research in mice shows that the sense of smell can also facilitate this so-called “social transfer” of pain. The study was published online October 19, 2016 in the journal Science Advances.
An unexpected finding
Monique Smith, working with Andrey Ryabinin at Oregon Health and Science University School of Medicine in Portland, Oregon, US, was initially interested in studying the pain that alcoholics experience during withdrawal, which is thought to increase the risk for relapse. To do so, she modeled this type of pain in mice by giving the animals access to alcohol, followed by a withdrawal period where no alcohol was available.
As predicted, animals undergoing alcohol withdrawal did experience increased levels of pain, as assessed by their sensitivity to pokes of the paw with a thin filament (a common experimental technique used in pain studies). Surprisingly, however, so too did control animals housed in the same room, but in different cages; these animals were not exposed to alcohol or withdrawal, and therefore should not have experienced pain.
(Control animals, which don’t receive the experimental manipulation—in this case, alcohol and withdrawal–are used in research to provide confidence that any result in the experimental group is indeed caused by the experimental manipulation).
To confirm the surprising result, Smith performed a similar study using two other mouse models of pain that are common in pain research, including pain resulting from morphine withdrawal, and pain from injection of an inflammatory substance. Again the researchers saw the same thing. That is, the experimental animals became sensitive to pain, as predicted. But so too did the control animals, who were again housed in the same room but in different cages, and were not subjected to morphine withdrawal or to inflammation.
“It was totally unexpected when the controls also developed pain,” said Ryabinin.
Seeking an explanation
How to explain this unanticipated result? Previous studies have shown that, just as in people, social interactions between mice can modulate the pain they feel. Yet the control mice in the current study were living in separate cages and couldn’t see the experimental mice.
To solve the mystery, Smith used a second control group that was housed in a room entirely separate from the experimental animals. This time, the controls didn’t experience any pain at all.
Somehow, then, the experimental animals communicated their pain to the control animals when both groups were in the same room, causing the controls to also experience pain.
Suspecting that scent might explain the finding, Smith scooped up dirty bedding from the cages of mice undergoing pain from alcohol withdrawal and put it into an empty cage that sat next to the control mice in the other room—the only animals that weren’t in pain. Within a day, these control mice developed pain.
In some fashion, then, the scent of the bedding from the animals undergoing pain from alcohol withdrawal caused the control animals to also act as if they were in pain.
“There is something in the bedding, but we really don’t know what it is,” Ryabinin said.
Although it’s appreciated that social interactions can affect pain, this study suggests that it’s not just visual or verbal cues that contribute to the social transfer of pain, but also scent.
It is important, however, to remember that the study used mice, which have a greater reliance on the sense of smell than humans do. So, it is still unclear whether scent plays a similar role in the social transfer of pain in people. —Nathan Fried
To read about the research in more detail, see the related Pain Research Forum news story here.
Nathan Fried is a postdoctoral fellow at the University of Pennsylvania, Philadelphia, US.