Why Some Pain Fades and Others Linger

Why does some pain fade while other pain lingers for months or years? A new study from researchers at the Hebrew University of Jerusalem reveals a built-in "brake" system in the brain that helps calm short-term pain — and shows what goes wrong when that system fails. Published in Science Advances, the study offers new insight into why chronic pain persists and points to potential new directions for treatment.

How the Brain Handles Pain

The research, 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, focused on a small area in the brainstem called the  medullary dorsal horn , where pain signals are relayed from the body to the brain. The team discovered that during acute (short-term) pain, these brain cells activate a kind of braking mechanism — they reduce their own activity to prevent pain signals from becoming overwhelming.

A Clue in Potassium Currents

The key to this difference lies in a specific electrical current in the brain, known as the A-type potassium current (IA). In acute pain, IA increases, helping calm the neurons. But in chronic pain, IA stays low — and the neurons spiral into overdrive.

Toward Better Pain Therapies

Chronic pain affects over 50 million people in the U.S. alone. Current treatments are often ineffective or come with serious side effects. The Hebrew University team’s discovery could help lead to smarter, more targeted pain therapies, giving hope to millions who live with ongoing pain.

 

But in cases of chronic (long-term) pain, that brake fails. The same cells become hyperactive, firing off more and more pain signals.

 

“This is the first time we’ve seen how the same neurons behave so differently in acute versus chronic pain,” said Prof. Alexander M. 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.”

“This is the first time we’ve seen how the same neurons behave so differently in acute versus chronic pain (...) If we can find a way to restore or mimic that braking system, we might be able to prevent pain from becoming chronic.”

Prof. Alexander M. Binshtok

 Reference: Title B, Velasco E, Engelmayer N, et al. Opposite regulation of medullary pain–related projection neuron excitability in acute and chronic pain. Sci Adv. 2025;11(25):eadr3467. doi: 10.1126/sciadv.adr3467

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