A parabrachial hub for need-state control of enduring pain, 2025, Goldstein et al.

Chandelier

Chandelier

Senior Member (Voting Rights)
www.nature.com

A parabrachial hub for need-state control of enduring pain - Nature

Activity in a set of parabranchial neurons in the mouse brain is increased during chronic pain, predicts coping behaviour, and can be modulated by circuits activated by survival threats.
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Abstract​

Long-term sustained pain following acute physical injury is a prominent feature of chronic pain conditions1.
Populations of neurons that rapidly respond to noxious stimuli or tissue damage have been identified in the spinal cord and several nuclei in the brain2–4.
Understanding the central mechanisms that signal ongoing sustained pain, including after tissue healing, remains a challenge5.

Here we use spatial transcriptomics, neural manipulations, activity recordings and computational modelling to demonstrate that activity in an ensemble of anatomically and molecularly diverse parabrachial neurons that express the neuropeptide Y (NPY) receptor Y1 (Y1R neurons) is increased following injury and predicts functional coping behaviour.

Hunger, thirst or predator cues suppressed sustained pain, regardless of the injury type, by inhibiting parabrachial Y1R neurons via the release of NPY. Together, our results demonstrate an endogenous analgesic hub at pain-responsive parabrachial Y1R neurons.
 
penntoday.upenn.edu

A built-in ‘off switch’ to stop persistent pain | Penn Today

J. Nicholas Betley has led collaborative research seeking the neural basis of long-term sustained pain and finds that a critical hub in the brainstem holds a mechanism for stopping pain signals from reaching the rest of the brain. Their findings could help clinicians better understand chronic...
penntoday.upenn.edu penntoday.upenn.edu

AI Summary:
Title: A Built-in Brain Switch to Silence Chronic Pain

Understanding Chronic Pain

Chronic pain affects nearly 50 million people in the United States. Unlike acute pain, which is short-lived and protective, chronic pain persists long after the original injury has healed. This ongoing pain can become a condition of its own, often without clear physical causes. According to neuroscientist J. Nicholas Betley, the problem may not lie in the body but within the brain itself, where pain signals continue to fire long after they’re needed.

Discovery in the Brainstem

Recent research led by Betley, in collaboration with scientists at the University of Pittsburgh and Scripps Research Institute, has identified a key area in the brainstem called the lateral parabrachial nucleus (lPBN). Within this region, they found neurons that express Y1 receptors (Y1R), which act as an internal "off switch" for persistent pain signals. These neurons are active during chronic pain but are also involved in processing hunger, fear, and thirst—suggesting they help prioritize the brain's response to competing needs.

How the Pain Signal is Blocked

Using calcium imaging in animal models, researchers discovered that Y1R neurons show continuous, or "tonic," activity during chronic pain states. Interestingly, stimuli like hunger, thirst, or fear can override this activity. The key mechanism involves neuropeptide Y (NPY), a molecule that interacts with Y1R neurons to reduce pain signaling when survival needs are more urgent. This finding suggests that the brain has a natural way of suppressing pain to focus on other critical tasks.

A Complex and Distributed System

The Y1R neurons are not isolated in one area but are scattered among different types of neurons. This distribution may allow the brain to regulate various forms of pain across different neural circuits. It also adds complexity to understanding and targeting these neurons for treatment.

Potential for New Treatments

This discovery opens new doors for treating chronic pain. By targeting Y1R neurons or using their activity as biomarkers, clinicians might better diagnose and treat pain that does not correspond to a clear injury. Additionally, the research supports the idea that non-pharmaceutical approaches—like exercise, meditation, and therapy—could influence how these brain circuits process pain.

A New Path Forward

The research suggests a future where pain management could involve both medical and behavioral interventions. Understanding the brain’s internal mechanisms for prioritizing needs over pain could lead to more effective and personalized treatments for chronic pain sufferers.
Click to expand...
 
Chandelier said:
Hunger, thirst or predator cues suppressed sustained pain, regardless of the injury type, by inhibiting parabrachial Y1R neurons via the release of NPY.
Click to expand...
If the results hold up, this doesn’t fit very well with the BPS models that claims that fear creates or amplifies chronic pain.

Edit: it seems like sustained pain in this context might mean pain induced by sustained input, and not pain without input from peripheral neurons.
 
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