A brain circuit linking pain and breathing may offer a path to prevent opioid deaths

Jon Hamilton

December 22, 2021 / 3:00 am

caption: Shell neurons (green) project to the breathing center and core neurons (red) project to the pain/emotion center. Brain scientists have found the two are linked, shedding new light on opioid overdoses

When people feel pain, they tend to breathe faster. When they take an opioid to ease that pain, their breathing slows. And if they overdose, respiration can stop entirely.

Now scientists have discovered a brain circuit in mice that appears to explain how opioids affect both pain and breathing, a team reports in the journal Neuron.

The team also found evidence that it's possible to separate these effects, potentially allowing for pain drugs that don't affect respiration.

If the finding holds up in people, "it's possible that we can develop safer analgesics," says Sung Han, the study's lead author and an assistant professor at the Salk Institute in San Diego.

That's a "really important goal" in a nation where opioid overdoses kill more than 100 people a day, says Dr. Kevin Yackle, a researcher at the University of California, San Francisco who was not involved in the study.

Breathing and pain are deeply linked

The connection between breathing rhythm and the emotional experience of pain and anxiety has been known for centuries.

During childbirth, labor pains are associated with accelerated breathing. Shocking or frightening experiences also cause faster respiration.

Han got a personal demonstration of this connection recently while taking a shower.

"I forgot to change the temperature and the cold water just suddenly came out and covered my entire body," he says. "And then I was breathing really fast."

Now, Han thinks he knows why.

Through a series of experiments with mice, Han and a team of researchers identified two populations of neurons, both found in the same small area of the brainstem.

"One population regulates pain and the other population regulates breathing," Han says. And the two populations appear to interact, he says, which explains how a painful experience can increase a person's breathing rate.

Searching for safer ways to alleviate pain

The finding has practical implications because both groups of brain cells — the ones for breathing and the ones for pain — respond to opioids.

Research in the past couple of years has shown that an opioid overdose can be fatal primarily because the drug shuts down neurons that usually tell the lungs to keep breathing.

But until now, scientists didn't know that these neurons interacted with the neurons that respond to the experience of pain.

"The connection between the two is still something that's very new," says Yackle, who studies the brain circuits involved in breathing.

Assuming that people also have separate populations of neurons involved in pain and breathing, Yackle says, it should be possible to develop opioid-like drugs that don't affect the brain cells that keep us alive.

The new study also could point the way toward better drugs to revive a person who has overdosed, Yackle says.

"The only way right now is to give someone an opioid receptor antagonist like naloxone," Yackle says.

That drug, also known as Narcan, is highly effective at restoring normal breathing. But because it blocks all opioid effects, it also can induce withdrawal symptoms, which may lead to more drug taking and another overdose.

A drug that only restored breathing would be a better option," Yackle says.