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.

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

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.

“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

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.

About the Research

The research paper titled “Opposite regulation of medullary pain-related projection neuron excitability in acute and chronic pain” is available in Science Advances and can be accessed at: https://www.science.org/doi/10.1126/sciadv.adr3467
DOI: 10.1126/sciadv.adr3467

Researchers:
Ben Title¹², Enrique Velasco¹³⁴, Nurit Engelmayer¹², Prudhvi Raj Rayi¹², Roy Yanai¹², Shmuel Hart¹², Ben Katz¹², Shaya Lev¹², Yosef Yarom²⁵, and Alexander M. Binshtok¹²

Affiliations:
¹ Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine
² The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem
³ Department of Cellular and Molecular Medicine, KU Leuven
⁴ VIB Center for Brain and Disease Research; Neuroscience in Physiotherapy (NiP), independent research group
⁵ Department of Neurobiology, The Institute of Life Sciences, The Hebrew University of Jerusalem

For a century, the Hebrew University of Jerusalem has been a beacon for visionary minds who challenge norms and shape the future. Founded by luminaries like Albert Einstein, who entrusted his intellectual legacy to the university, it is dedicated to advancing knowledge, fostering leadership, and promoting diversity. Home to over 23,000 students from 90 countries, the Hebrew University drives much of Israel’s civilian scientific research, with over 11,000 patents and groundbreaking contributions recognized by nine Nobel Prizes, two Turing Awards, and a Fields Medal. Ranked 81st globally by the Shanghai Ranking (2024), it celebrates a century of excellence in research, education, and innovation. To learn more about the university’s academic programs, research, and achievements, visit the official website at http://new.huji.ac.il/en.