A new study from the Hebrew University of Jerusalem has uncovered why some pain fades while other pain lingers, sometimes becoming a chronic condition. The research reveals that, when we experience short-term (acute) pain, the brain has a built-in system to dampen pain signals—much like pressing the brakes—to prevent them from overwhelming the body. However, in cases of long-term (chronic) pain, this braking system fails, allowing pain signals to continue unchecked. This discovery sheds light on why some pain resolves while other pain persists, and opens the door to new treatments that could prevent pain from becoming chronic.
The Brain’s Pain Relays: Acute vs. Chronic Pain
Published this week in Science Advances, the study was led by doctoral student Ben Title under the supervision of Professor Alexander M. Binshtok from the Hebrew University-Hadassah School of Medicine and the Edmond and Lily Safra Center for Brain Sciences (ELSC). The team explored how the body responds to acute and chronic pain at the cellular level, focusing on a small but crucial region in the brainstem known as the medullary dorsal horn. This area contains neurons that act as relay stations, transmitting pain messages from the body to the brain.
The researchers discovered that during acute inflammatory pain, these neurons actually reduce their activity. This natural “braking system” helps to limit the volume of pain signals reaching the brain. Once the inflammation subsides, the neurons return to their normal state. In chronic pain, however, this braking mechanism fails. The neurons remain highly excitable, firing more signals and potentially contributing to the persistence of pain.
The Key Mechanism: A-Type Potassium Current
Using a combination of electrophysiology and computer modelling, the researchers identified a crucial 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 as a natural sedative for pain pathways. In chronic pain, however, this current does not rise, leaving the neurons hyperactive. The absence of this regulatory mechanism may be a key biological switch that transforms temporary pain into a long-lasting condition.
Implications for the Treatment of Chronic Pain
Chronic pain affects over 50 million people in the United States alone, often with limited effective treatment options. This new research adds a vital piece to the puzzle by demonstrating how the nervous system’s inherent pain controls are disrupted in chronic pain conditions.
“This is the first time we have observed how the same neurons behave so differently in acute versus chronic pain,” said Professor 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 this braking system, we may be able to prevent pain from becoming chronic.”
By understanding the brain’s own strategies for limiting pain—and why they sometimes fail—scientists are now one step closer to developing more precise and effective therapies for those suffering from chronic pain.
The research paper, “Opposite regulation of medullary pain-related projection neuron excitability in acute and chronic pain,” is now available in Science Advances: Read the full article Here
Researchers:
Ben Title, Enrique Velasco, Nurit Engelmayer, Prudhvi Raj Rayi, Roy Yanai, Shmuel Hart, Ben Katz, Shaya Lev, Yosef Yarom, and Alexander M. Binshtok
Institutions:
- Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine
- The Edmond and Lily Safra Center for Brain Sciences, Hebrew University of Jerusalem
- Department of Cellular and Molecular Medicine, KU Leuven; VIB Center for Brain and Disease Research
- Neuroscience in Physiotherapy (NiP), independent research group
- Department of Neurobiology, The Institute of Life Sciences, Hebrew University of Jerusalem