Summary: A new study reveals that neurons in the brainstem respond very differently to acute versus chronic pain, potentially explaining why some pain persists long after injury. In acute pain, neurons in the medullary dorsal horn reduce their activity through a natural “braking” system involving A-type potassium currents, helping limit pain signals.
But in chronic pain, this mechanism fails, and the neurons become overactive, continuing to send pain messages. This discovery provides a clearer biological pathway for how pain becomes chronic and may guide future therapies aimed at restoring this internal regulation system.
Key Facts:
- Brainstem Relay Dysfunction: In chronic pain, neurons in the medullary dorsal horn lose their ability to dampen pain signals.
- A-Type Potassium Current (IA): This current acts as a brake in acute pain but fails to activate in chronic pain conditions.
- Therapeutic Implication: Targeting IA could be a novel strategy to prevent or treat chronic pain.
Source: Hebrew University of Jerusalem
Why does some pain go away while other types linger, turning into chronic suffering?
A groundbreaking study from scientists at The Hebrew University of Jerusalem may have uncovered part of the answer — deep inside the brainstem.
In a study published this week in Science Advances, researchers led by Doctoral student Ben Title under the guidance of Prof. Alexander M. Binshtok from The Hebrew University-Hadassah School of Medicine and the Center for Brain Sciences (ELSC) at The Hebrew University, reveal that our bodies respond to acute (short-term) and chronic (long-lasting) pain in surprisingly different ways at the cellular level.
Their discovery sheds new light on how pain becomes chronic — and opens the door to better-targeted treatments.
The Brain’s “Pain Relays” Behave Differently in Acute vs. Chronic Pain
The team studied a small but crucial region in the brainstem called the medullary dorsal horn, home to neurons that act as a relay station for pain signals. These projection neurons help send pain messages from the body to the brain.
The scientists found that during acute inflammatory pain, these neurons actually dial down their own activity. This built-in “braking system” helps limit the amount of pain-related signals sent to the brain. Once the inflammation and pain subside, the neurons return to their normal state.
However, in chronic pain, this braking system fails. The neurons don’t reduce their activity — in fact, they become more excitable and fire more signals, potentially contributing to the persistence of pain.
The Key Player: A-Type Potassium Current
Using a combination of electrophysiology and computer modeling, the researchers identified a key mechanism: a specific potassium current known as the A-type potassium current (IA). This current helps regulate the excitability of neurons.
In acute pain, IA increases — acting like a natural sedative for the pain pathways. But in chronic pain, this current doesn’t ramp up, and the neurons become hyperactive. The absence of this regulation may be one of the biological switches that turns temporary pain into a long-lasting condition.
Implications for Chronic Pain Treatment
“This is the first time we’ve seen how the same neurons behave so differently in acute versus chronic pain,” said Prof. Binshtok.
“The fact that this natural ‘calming’ mechanism is missing in chronic pain suggests a new target for therapy. If we can find a way to restore or mimic that braking system, we might be able to prevent pain from becoming chronic.”
A Step Toward Smarter Pain Therapies
Chronic pain affects over 50 million people in the U.S. alone, often with few effective treatment options. This new study adds an important piece to the puzzle by showing how the nervous system’s built-in pain controls are disrupted in long-term pain conditions.
By understanding the brain’s own strategies for limiting pain — and why they sometimes fail — scientists are now one step closer to developing smarter, more precise therapies for those who suffer from chronic pain.
About this pain and neuroscience research news
Author: Danae Marx
Source: Hebrew University of Jerusalem
Contact: Danae Marx – Hebrew University of Jerusalem
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Opposite regulation of medullary pain-related projection neuron excitability in acute and chronic pain” by Alexander M. Binshtok et al. Science Advances
Abstract
Opposite regulation of medullary pain-related projection neuron excitability in acute and chronic pain
Pain hypersensitivity is associated with increased activity of peripheral and central neurons along the pain neuroaxis.
We show that at the peak of acute inflammatory pain, superficial medullary dorsal horn projection neurons (PNs) that relay nociceptive information to the parabrachial nucleus reduce their intrinsic excitability and, consequently, action potential firing.
When pain resolves, the excitability of these neurons returns to baseline.
Using electrophysiological and computational approaches, we found that an increase in potassium A-current (IA) underlies the decrease in the excitability of medullary dorsal horn PNs in acute pain conditions.
In chronic pain conditions, no changes of IA were observed, and medullary dorsal horn PNs exhibit increased intrinsic excitability and firing.
Our results reveal a differential modulation of the excitability of medullary dorsal horn projection neurons in acute and chronic pain conditions, suggesting a regulatory mechanism that, in acute pain conditions, tunes the output of the dorsal horn and, if lacking, could facilitate pain chronification.
