For roughly 20% of Americans, chronic pain is a relentless part of life, often managed only with a slew of medications and a reduction in daily activities.

Among the 51 million adults grappling with chronic pain, recent surveys indicate that around 75% experience some form of disability, severely impacting their ability to work or carry out normal functions.

The origins of chronic pain, whether it affects shoulders, backs, knees, or feet, have long been a subject of debate, with no definitive conclusion. However, researchers at the University of Colorado at Boulder may have uncovered an important clue.

In their latest study, the researchers set out to explore how temporary, or acute, pain transitions into chronic pain. They focused on a neural pathway in the brain connecting the caudal granular insular cortex (CGIC), a small cluster of cells within the insula responsible for processing bodily sensations, to the primary somatosensory cortex, which interprets pain and touch.

The study utilized mice to replicate chronic pain conditions affecting the sciatic nerve, the body’s longest and largest nerve, which runs from the lower spine to the feet. Damage to the sciatic nerve is known to cause allodynia, a condition where normally non-painful touch becomes painful.

Through gene editing techniques that disabled specific neurons, the researchers discovered that while the CGIC had a minimal role in processing acute pain, it communicated with other brain regions responsible for pain perception, instructing the spinal cord to maintain chronic pain.

Inhibiting cells in the CGIC pathway, meanwhile, reduced the mice’s pain and stopped their allodynia.

The experts believe while the findings are still new, they may pave the way for future medications and treatments to target CGIC and eliminate chronic pain. 

Researchers at the University of Colorado at Boulder have found a pathway that may be a cause of chronic pain (stock image)

Linda Watkins, senior study author and distinguished professor of behavioral neurosciences at the University of Colorado at Boulder, said: ‘Our paper used a variety of state-of-the art methods to define the specific brain circuit crucial for deciding for pain to become chronic and telling the spinal cord to carry out this instruction.

‘If this crucial decision maker is silenced, chronic pain does not occur. If it is already ongoing, chronic pain melts away.’ 

Back pain, headaches and migraines and joint conditions such as arthritis are the most common forms of chronic pain in the US, resulting in nearly 37 million doctor appointments every year.

And about one in three American adults with chronic pain report not having a clear diagnosis or reason behind it. 

The new study, published last month in The Journal of Neuroscience, looked at mice given injuries to their sciatic nerves. Pain in this area is called sciatica, which affects about 3 million Americans. 

The team then measured how sensitive their paws were to touch and looked at brain and spinal cord activity to evaluate pain.

They found that the CGIC sends widespread signals to the primary somatosensory cortex. This is located in the brain’s parietal lobe, which processes sensory information such as touch, temperature, pain and pressure. CGIC activation resulted in chronic pain. 

Jayson Ball, first study author and scientist at brain health startup Neuralink, said: ‘We found that activating this pathway excites the part of the spinal cord that relays touch and pain to the brain, causing touch to now be perceived as pain as well.’

The above CDC graph shows the percentage of adults who have experienced chronic pain and high-impact chronic pain, which significantly limits daily life, in the past three months. The figures are from 2023, the latest available

The researchers then used gene editing to suppress CGIC activity, which resulted in reduced activity in the mice’s brains and spines, even in mice that had suffered pain for several weeks at a time, the equivalent to years for a human.  

Ball said: ‘This study adds an important leaf to the tree of knowledge about chronic pain.

‘Our research presents a clear case that specific brain pathways can be directly targeted to modulate sensory pain.’ 

The researchers said additional studies are needed to understand the relationship between CGIC and chronic pain, particularly in humans rather than mice.

Watkins said: ‘Why, and how, pain fails to resolve, leaving you in chronic pain, is a major question that is still in search of answers.’ 

However, Ball noted that the findings may pave the way for developing medications that target CGIC. 

He said: ‘Now that we have access to tools that allow you to manipulate the brain, not based just on a general region but on specific sub-populations of cells, the quest for new treatments is moving much faster.’