Weekly blog

Oct 17

Pain is a universal human experience and, at the most basic biological level, a critical warning system that lets us know when it's best to "stop everything" to avoid danger. Yet, as we've learned in greater detail over the last few decades, it isn't just a "local" danger radar, like the temperature sensors activated when we touch a hot stove, but rather, a finely tuned brain-integrated system which uses our past experiences to help predict our current and future risk. Unfortunately, there are times when our memory doesn't quite fade like it should and the system gets stuck in the "on" position, allowing our brain to send continuous full volume pain warnings long after healing has taken place or, as in cases of phantom limb pain (the experience of pain in a limb that has been amputated), the local signal has been turned off.

This can be just as confusing and frustrating as it sounds. While the initial pain might have been turned on locally with the onset of injury, it ultimately "lives" in the activated circuits of our brain. Therefore, what we experience as very real pain, often at the site of an old injury long after healing and even without any active harm present, is more likely to be a stuck brain switch. Referred to as persistent pain and impacting as many as 50 million Americans, this type of overreaction by our warning system can become a major impact on quality of life.

The good news is, as experts have helped us transition from dismissing something that we don't understand ("it's not real") to searching in the right places ("because it lives in the brain, it is both a mind and body phenomenon"), we have learned a ton. For example, while we know it is more likely to occur in individuals who experience chronic stress at a young age (especially those with adverse childhood experiences), we also know that lifestyle and health habits play an important role. For example, there is a known association between metabolic disease and persistent pain (possibly related to inflammation), and the emerging evidence shows that improving health factors can lower the odds of persistent pain. 

For example, in one study from earlier this year, individuals with knee pain who maintained a healthy lifestyle were significantly less likely to experience chronic pain than less health-focused counterparts over the two-year study period. Similarly, in a 2025 randomized trial, back pain sufferers who improved their health habits showed a greater recovery than those who performed more traditional (guideline-based) care without an emphasis on lifestyle habits. Now, in a very interesting development last week, we may be closer to understanding why.

As published in the journal Nature, a UPENN neuroscientist who had personally observed that being really hungry dampened chronic pain, found the root of this phenomenon. As it turns out, a bundle of nerves in the brain stem that plays an important role in driving the chronic pain experience also relates to other key survival circuits such as thirst and fear. The team went on to find a specific signaling molecule called Neuropeptide Y (NPY), which helps the brain juggle these competing needs and override pain in the face of more critical needs. 

“It’s like the brain has this built-in override switch. If you’re starving or facing a predator, you can’t afford to be overwhelmed by lingering pain. Neurons activated by these other threats release NPY, and NPY quiets the pain signal so that other survival needs take precedence”.

 While there's still plenty of work to be done to develop a treatment for this overactive circuit, the team has made it clear that they hope for more than a pill. “We’ve shown that this circuit is flexible; it can be dialed up or down, so the future isn’t just about designing a pill. It’s also about asking how behavior, training, and lifestyle can change the way these neurons encode pain”.

Pain that lasts for more than 90 days can be frustrating and confusing. The good news is, it doesn't always have to be. Reach out if we can help.

Have a great weekend,
Mike E.