Researchers Investigate Natural Pain Killing Circuit in the Brain

Lead researcher Ben Seymour, PhD, noted that this brings medicine a step closer to harnessing the brain's natural pain relief system in a more specific way.

Ben Seymour, PhD

When thinking of painkillers, more often than not, the mind settles on opioids—the drugs at the heart of a current overdose epidemic in the United States. But the body has its own, natural pain-killing mechanisms as well, and a recent study by researchers at the University of Cambridge and the Advanced Telecommunications Research Institute International in Japan has shed light on how this natural pain-killing circuit is activated in the brain.

The study authors hope that the information will help researchers understand what goes wrong in patients with chronic pain, and possibly lead to safer and more effective treatments. Scientists know very little about how we feel and reduce pain naturally, and the mechanisms of existing treatments are poorly understood.

“We recognize that persistent pain (e.g. after injury) is a valuable signal—it tells us to stop doing other things, and rest and recuperate,” Ben Seymour, PhD, a neuroscientist at the University of Cambridge and the leader of the study, told MD Magazine. “But more subtly, there may be times when it makes sense to turn it down—for instance when the opportunity arises to try and find ways to reduce it—and that's the idea at the heart of this: can we identify a brain circuit that reduces pain in certain situations?”

In the study, 42 healthy volunteers were set up with a metal probe touching their arm, which would then be heated to a temperature that was painful, but that would not burn the participant. Once heated, the patients were presented with several buttons, 1 of which would cool the probe and decrease their pain. In some of the trials, the patients had to figure out which button would ease the pain. In other trials, the participants already knew while which button to push.

During each trial, researchers used functional magnetic resonance imaging (fMRI) to scan the participants’ brains and took subjective reports of how much pain they were feeling throughout.

When they were trying to figure out which button to push, participants said their pain decreased, even though the probe did not change temperature. However, when the participants already knew which button to push, their pain remained unchanged—the brain was balancing the pain with the need to focus on learning how to relieve it.

The brain scans helped the team identify a circuit that seemed to control both pain suppression and the learning that helps patients escape the pain. They noticed activation in a particular area of the brain—the pregenual cingulate cortex. The researchers deemed this the “decision center,” that determines if the brain turns on its natural pain-killing circuit.

Next, the researchers hope that they can begin to identify the molecular components of the circuit to identify new drug targets. They also hope to explore whether non-drug treatments such as neurofeedback or deep brain stimulation may be effective.

“It takes us 1 step closer to being able to harness the brain's natural pain relief system in a more specific way than just giving opioids,” he said. “Putting together the brain circuits is really crucial basic science that we need to get in place to make eventual progress on the clinical front.”

The study, “The control of tonic pain by active relief learning,” was published in eLife.

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