Pain is an important biological mechanism. It tells us when something in our body is damaged, and forces us into inactivity so energy can be diverted to healing. But sometimes pain can be counter-effective, hindering a person's ability to actively help themselves, so the brain effectively "turns down" those pain signals so relief can be effectively found. New research has identified where in the brain this natural painkilling system is controlled from, suggesting new pathways toward non-opioid painkillers.

In 2017, the US Department of Health and Human Services declared the ongoing opioid crisis in the country as a public health emergency. The rate of opioid overdose deaths in 2016 were five times higher than in 1999. Research into alternative methods of pain control has never been more important than right now and scientists are investigating a variety of different targets, from tricking the body's pain-signaling pathways at the site of an injury to studying people with unique genetic mutations that make them feel no pain.

This new research, led by scientists at the University of Cambridge, set out to understand how the brain actively regulates pain in the body through the endogenous analgesia system that can seemingly "turn down" pain signals. The team devised a pair of experiments designed to home in on the parts of the brain that modulate the degree of pain felt throughout the body.

"We're trying to understand exactly what the endogenous analgesia system is: why we have it, how it works and where it is controlled in the brain," says Ben Seymour, lead on the research project.

The first experiment subjected volunteers to an external source of painful heat on their arm that could be reduced by playing a game that led them to press a specific button. The degree of difficulty in the game varied and the volunteers constantly rated their pain levels while having their brain activity monitored.

The fascinating results revealed that pain levels were identified as lower when a subject was actively working to target the right button, but pain was not reduced when the subject knew which button to press. This meant that a part of the brain was modulating the degree of pain felt depending on how actively the person was working on finding a solution to reducing the source of the pain.

The subsequent experiment was to find where exactly in the brain this pain-modulating signal was coming from. A very specific target was identified in a small part of the prefrontal cortex – the pregenual cingulate cortex.

"These results build a picture of why and how the brain decides to turn off pain in certain circumstances, and identify the pregenual cingulate cortex as a critical 'decision centre' controlling pain in the brain," says Seymour.

The exciting conclusion is that this area of the brain could actively reduce the sensation of pain temporarily in situations where that pain is hindering a person from successfully doing something that could help. Future research will look at what inputs are activating this brain region and whether there are ways to artificially stimulate it, in the hopes of developing a new treatment for patients with chronic pain.

"If we can figure this out, it could lead to treatments that are much more selective in terms of how they treat pain," adds Seymour.

The research was published in the journal eLife.