Painkillers: Scientists Figured Out How to Decouple Pain From Suffering

"They still have the sensation, but they don’t seem to care about it anymore."

It’s hard to hear the word pain without thinking of suffering. It’s even harder to imagine that it might be possible to experience a pinprick or a scalding hot water without feeling bad about it, though the authors of a new Science paper believe it’s possible. By changing the behavior of a few cells in the brain, they are reshaping the experience of pain.

They hope that doctors may someday be able to intervene in the messaging system that the brain and body uses to communicate pain in order to stop it from feeling so bad. It’s a simple system: A stimulus activates nerves in a part of the body that’s under attack, and those nerves send messages to the brain. The brain reads those messages and interprets them, producing the negative emotional sensation that accompanies the physical sensation of pain.

The paper’s authors, Grégory Scherrer, Ph.D., an assistant professor of anesthesiology and neurosurgery at Stanford, and Mark Schnitzer, Ph.D., an associate professor of biology and of applied physics, also at Stanford, want to disrupt this messaging system so that patients still feel the sensation of pain but don’t suffer as a result of it.

"“So in contrast to opioids you could decrease pain but without causing any dependence."

“We wanted to be more precise here and identify the region and the cells that are responsible for pain unpleasantness,” Scherrer tells Inverse. “We thought if we could find the center, or the cells in the brain that make pain unpleasant, perhaps acting on these cells could be a good strategy to reduce pain in chronic pain patients.”

By targeting cells associated with pain's unpleasant sensation, Scherrer and Schnitzer think we can develop new types of pain medication.

Unsplash / Issam Hammoudi

The Cells Responsible for Pain’s Unpleasantness

It’s already established that the amygdala plays a role in the emotional component of pain, but this team actually found the exact cells in the amygdala responsible for those unpleasant pain messages by using a “miniscope,” a tool created by Schnitzer, and observing how mice responded to painful stimuli.

When mice in their experiment were exposed to a drop of scalding water, a given a pinprick, or asked to run along unpleasantly hot tracks, these cells in the amygdala were highly active. Importantly, Schnitzer adds, they didn’t light up when the mice were exposed to other stimuli like sugar water or a bad smell. “Every time mice were unpleased with the stimulation, we saw that these cells were turned on,” he adds.

In a follow-up experiment, Scherrer and Schnitzer temporarily disabled those cells and exposed the mice to hot temperatures, water droplets, or pinpricks. When confronted with pinpricks and water droplets, the mice still pulled their paws away, but in a more calm and controlled fashion.

That motion, Scherrer explains, is a natural “withdrawal reflex” similar to what you might feel in the milliseconds after you inadvertently place your hand on a hot stove:

“When you’re cooking in the kitchen and you’re distracted, you put your hand on the stove you don’t even have the time to think of your pain, but you’ve already withdrawn from the stimulus,” Scherrer says. “So this is intact in these mice when we turn off these cells. They still have the sensation, but they don’t seem to care about it anymore.”

A Drug for Pain Management?

The team hopes that these cells will be potential targets for a drug to manage pain. That drug would manipulate the behavior of those cells so you’re aware of the “noxious stimuli” — you would even feel something — but it’s just not a bad feeling.

That said, it’s not a good feeling either. Crucial to their approach is the idea that the mice in the study retained their “withdrawal reflex” — which indicates that there’s still some sort of messaging going on. The idea is that all pain would be like the “pain” experienced in those microseconds between when you touch the hot stove and when you pull your hand away without thinking about it.

Opioid drugs have high potential for abuse because they also affect the brain's reward systems. 


That lack of a good feeling is even more important, given the recent history with pain management drugs. Opioids — the most infamous class of pain management drugs — attach to opioid receptors in the brain or spinal cord, which block the reception of pain messages, but they also bind to receptors that are part of the brain’s reward system. That lack of preciseness can make them devastatingly addictive.

“What we found is that these cells don’t seem to be active or important for reward in our study,” says Scherrer. “The goal is we can find a receptor in a future study that is present in these cells but is not present in the reward system. So in contrast to opioids you could decrease pain but without causing any dependence.”

The trick will be to find a receptor that can actually accomplish that job. By identifying these cells Scherrer and Schnitzer have identified a good place to search for one. They’re in search of a target on these cells that is truly unique to them, and a drug that exclusively binds to it. If opioids taught us anything, it’s that specificity is crucial.

They find that target, their drug could create a sensation so unique that we don’t even really have a word for it: pain without unpleasantness (maybe numbness?). That’s a long way off, but these cells are a start.

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