The mice should not have been feeling pain.
Their hind paws were being touched with filaments so thin that most mice would hardly notice the tickle. Yet these animals reacted as if their paws were on fire.
Now, neuroscientists have an explanation: the mice caught their hypersensitivity to pain the way you catch a common cold. A paper published Wednesday in Science Advances shows that lab mice living in the same room as those who are primed to feel more pain end up taking on their roommates’ heightened susceptibility. How could such contagion happen? By smell, the researchers say.
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Not all pain specialists are convinced. But if the finding is borne out by other studies, it could mean that almost every mouse lab on the planet needs to rethink its interior design. Scientists, and clinicians, have long understood that pain can be socially modulated. They just didn’t think the social contagion of pain might be strong enough to skew experimental results.
Researchers are now wondering whether past studies might have overlooked some mice’s pain because their roommates — with which they were being compared — had taken on their level of sensitivity. That could have influenced research on everything from drug withdrawal to painkillers.
“This is something that most — if not all — researchers are not taking into account,” said Loren Martin, a pain researcher at the University of Toronto Mississauga who was not involved in the new study.
Andrey Ryabinin, the lead author of the paper, wasn’t intending to study the social transmission of pain. His neuroscience lab at Oregon Health and Science University focuses on alcoholism.
He and a graduate student were looking into one of the frustrating facts of doing addiction research on rodents: namely, that alcohol withdrawal makes humans feel pain more acutely, but no one had been able to document the same phenomenon in mice. Yet when the researchers tested the idea, they found that the mice in withdrawal were in fact more sensitive to pain than they had been before they got hooked on alcohol. Scientists just hadn’t noticed because the same was true of the non-addicted mice that were being used as a comparison group.
“I was in disbelief myself,” said Ryabinin. “I was ready to dismiss this, I was saying, ‘Something is wrong here.’”
His grad student convinced him to keep digging. So the team created three groups of mice. They primed some to feel pain more acutely, either by inducing withdrawal from opioids or alcohol, or by injecting them with an oil that causes soreness. The others were left as is; part of this group lived in the same room as the unlucky few made more sensitive to pain, while the rest got their own separate vivarium.
Then, the researchers performed standard tests developed to measure mouse pain. They poked paws with filaments, increasing the pressure with each poke and seeing when the mice flinched. They put tails in hot water and measured how long it took the rodents to flick them out. They injected paws with an irritant and watched how often the mice licked their wounds.
Living in the same room as a mouse in withdrawal, it turns out, lowers pain tolerance as much as drug or alcohol withdrawal itself. The mice kept in another room, on the other hand, stayed hardy, waiting longer before they felt the need to withdraw or lick their paw, or flick their tail out of harm’s way.
Ryabinin wanted to know more. What was causing the pain to sweep around the room like an infectious disease? Was it transmitted visually? Were mice hearing unhappy squeals that they internalized? Or were they picking up on the stink of pain?
“The easiest sense to test is the olfactory sense,” said Ryabinin. “We took some of the bedding from the animals that were undergoing withdrawal and put it in a completely different room. And these animals [in the different room] also showed increased pain sensitivity, actually to the level that it was not distinguishable from the animals in withdrawal.”
These stark results made some other researchers skeptical.
“If these effects really are this large, it’s really surprising that it has gone unnoticed until now,” said Martin. He also noted that the tests were performed in the room where the animals live, which could contribute to the transfer of pain.
The implications don’t just apply to lab mice. If the same is true of humans — a big if — then pain doctors may want to talk not just to their patients, but to their families and roommates, too. “If you are living with a chronic pain patient, what’s the impact on you?” asked Martin.
Robert Kerns, a Yale pain researcher and a former national director of pain management for the Department of Veterans Affairs, warned that mouse studies cannot necessarily be applied to people.
To him, though, this study underlines the idea, widely accepted among specialists, that a patient’s emotional and social context contribute to pain.
“It’s problematic to say that somebody’s pain is not real, or it’s psychological, just because we haven’t developed the technology to uncover or understand the biological contributors,” he said. “It’s critically important for the clinician … to show respect for their experience of pain, and to acknowledge the limits of biomedical science.”