Scientists have discovered a brain “pain switch” that prioritises survival needs over chronic suffering. This discovery could lead to new hope for pain relief specifically in the form of personalised treatments that target pain at its brain source.
Chronic pain is where the pain warning signal does not stop even after the injury has healed. The condition can persist for years or even decades and it occurs due to a brain input that has become sensitised and hyperactive.
Overriding chronic pain
This discovery, from the University of Pennsylvania, has come about by pinpointing Y1 receptor neurons in the brain (located in the lateral parabrachial nucleus (lPBN)). These cells can override chronic pain signals, suggesting that the brain can adjust pain responses when other, more urgent needs demand attention.
This occurs, for example, when survival instincts like hunger or fear take precedence. Acting like a neural switchboard, these cells balance pain with other biological needs.
the first phase of the research found that Y1R neurons do not simply react to quick bursts of pain; instead, they keep firing steadily during prolonged pain, a phenomenon known as “tonic activity.” As an analogy, this is like keeping the engine of a car running after it has been securely parked.
Through studies, the scientists showed that the brain’s parabrachial nucleus (which relays sensory information) can filter sensory input to quiet pain when immediate survival takes priority.
On-off switch
The question which followed is which part of the brain is responsible for the on-off switch. It was identiifed that a key part of that switch is neuropeptide Y (NPY), a signalling molecule that helps the brain juggle competing needs. When hunger or fear takes priority, NPY acts on Y1 receptors in the parabrachial nucleus to dampen ongoing pain signals.
As a ‘natural instinct, if a person is starving or facing a predator, they cannot afford to be overwhelmed by lingering pain. Hence, neurons activated by these other threats release NPY, and NPY quiets the pain signal so that other survival needs take precedence.
The researchers also characterized the molecular and anatomical identity of the Y1R neurons in the lPBN. They found that Y1Rneurons didn’t form two tidy anatomical or molecular populations. Instead, these neurons were scattered across many other cell types.
Going forwards
For future research, the scientists hope to use Y1 neural activity as a biomarker for chronic pain, something drug developers and clinicians have long lacked.
the answer may also not be simply down to a future drug for the research also suggests that behavioural interventions such as exercise, meditation, and cognitive behavioural therapy may influence how these brain circuits fire.
The research appears in the journal Nature, titled “A parabrachial hub for need-state control of enduring pain.”
