Deep in the brain, in a region until now discreetly ignored by pain science, a small army of neurons has raised new hope. This is a specific group of brain cells that remain active long after the body has suffered an injury.

The finding, made in mice by researchers at the University of Pennsylvania, not only identifies the neuronal epicenter of chronic pain, but also suggests that the brain holds within itself the key to silence it. If the results are replicated in humans, we could be facing one of the most promising advances in the treatment of persistent pain.

Globally, it is estimated that one in five people lives with some type of chronic pain, an experience that is often invisible but absolutely real. “The pain is in your head. But it is very real,” emphasizes Nicholas Betley, one of the authors of the study published in Nature. His team has focused its attention on the parabranchial nucleusa brain region that acts as a communications center between the body and mind.

In the study, a subset of neurons distributed throughout this nucleus was identified that activate after an initial painful stimulus (such as a cut or nerve damage) and remain on for days or even weeks, as sentinels of suffering that no longer responds to an external cause. These neurons carry neuropeptide receptors. And, a molecule that has turned out to be key in modulating persistent pain.

A pain switch

The experiments revealed something as disturbing as it was promising: by artificially activating these neurons, the mice developed behaviors associated with pain. But by inhibiting them, chronic pain decreased significantly, while responses to acute pain remained intact: that useful pain that protects us from immediate dangers such as heat or a recent injury.

Interestingly, mice with persistent pain also reacted differently when their vital needs conflicted with pain. If they were hungry, thirsty, or exposed to an odor that evoked danger (such as lynx urine), they displayed behaviors that indicated a reduction in pain. As if the brain, subjected to a higher priority, reconfigured its threshold of suffering in order to survive..

This phenomenon would be explained by the release of neuropeptide Y from other brain areas, which upon reaching the parabranchial nucleus, turns off (at least temporarily) the chronic pain neurons.

The plasticity of pain

This plasticity of pain has been, for years, one of the great unknowns of neuroscience. Why do some people continue to suffer years after an injury? What makes pain become part of the mental landscape? The study suggests that the parabranchial nucleus could be a kind of control tower for suffering, where it is decided whether the pain continues or fades, depending on the context.

However, it is worth being cautious. Measuring chronic pain in animals soon after an injury may not fully reflect what happens in humans, where pain can persist for months or years. Even so, he believes that this type of research could pave the way to a deeper understanding of the phenomenon.

Implications

The therapeutic possibilities that open up are multiple. From drugs that modulate neuropeptide Y signaling to more natural strategies such as meditation, acupuncture or even deep brain stimulation could one day target silencing these specific neurons in the parabranchial nucleus.

Betley highlights an additional aspect: the possibility of using the activity of these neurons as an objective biomarker of chronic pain, which could revolutionize both diagnosis and the effectiveness of treatments. “You can’t ask an animal if it feels better. But now we could observe if the activity of these neurons decreases with therapy.”