Cell Defense Meant to Protect Triggers Chronic Pain... Korean Team First to Reveal Mechanism [Reading Science]

Nobel Prize-winning Study Reveals New Role of 'Piezo', Suggesting Fundamental Treatment Strategies
Published in World-renowned Journal 'Cell'
New Hope for Treating Cystitis and Irritable Bowel Syndrome

The underlying mechanisms behind refractory chronic pain conditions, such as chronic cystitis—which causes severe pain even with the slightest touch—and idiopathic irritable bowel syndrome, have been revealed for the first time in the world by a Korean research team. It was confirmed that the cell defense system, which normally functions to protect our bodies, can instead create new pain nerves and thus sustain chronic pain. This opens up the possibility for the development of fundamental treatment strategies.

On June 30, Korea University announced that a research team led by Professor Haeung Choi of the Department of Life Sciences has identified a new biological mechanism by which the pressure-sensing protein 'Piezo (PIEZO)' induces chronic pain. The research findings were published in the world-renowned life science journal ‘Cell’.

When the pressure-sensing protein Piezo is excessively increased due to repeated inflammation, glutamate is secreted during the cellular defense process, stimulating pain nerves and creating new nerve branches, leading to chronic pain. Provided by the research team

Nobel-winning Research on 'Piezo': The Key to Chronic Pain

Piezo is a mechanosensitive ion channel protein that enables cells to detect physical stimuli such as pressure or stretching. It was a central topic in the research that won the Nobel Prize in Physiology or Medicine in 2021.

The research team found that when inflammation occurs repeatedly in the epithelial cells of the bladder and intestines, Piezo becomes excessively activated, leading to the accumulation of oxidative stress within the cells.

To protect themselves, cells activate a defense protein called ‘SLC7A11’. However, this process has the side effect of causing the neurotransmitter glutamate to be secreted excessively outside the cell. This released glutamate then stimulates surrounding pain nerves, promoting the growth of new pain nerve branches into the tissue, ultimately resulting in a state where severe pain persists even in response to minor stimuli.

The research team presented this entire process as a new mechanism for chronic pain development, which they termed 'epithelial-neural rewiring'.

Beyond Analgesics: Toward Fundamental Treatments

In animal experiments, the research team found that inhibiting the activity of SLC7A11, which plays a key role in the pain induction process, reduced the proliferation of pain nerves and significantly improved urinary dysfunction.

Research team photo. Professor Choi Haewoong of Korea University (left) and Kim Minjung, Ph.D. candidate at Korea University. Courtesy of Korea University

The team explained that these results suggest the possibility of developing new treatment strategies that target the root causes of chronic pain, rather than merely providing temporary relief as existing analgesics do.

In particular, since Piezo is present not only in the bladder but also in most tissues of the body, including the intestines, lungs, joints, and skin, this research is expected to contribute to the development of therapeutics for various refractory chronic pain conditions, such as irritable bowel syndrome, chronic pelvic pain, and fibromyalgia.

Professor Choi stated, “This study elucidates how the basic biological phenomenon of cells sensing mechanical forces leads to disease. We hope it paves the way for new treatment strategies that target the root causes of chronic pain.”

This content was produced with the assistance of AI translation services.