The Editors in chief of GUT, Professors Matias A. Avila, William Grady and Thomas Rösch, have selected Professor Rui Li, Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China and Professor Guang-Yin Xu from the same institution as well as the Clinical Research Center of Neurological Disease, Second Affiliated Hospital of Soochow University, Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience and the Biomedical Basic Research Center (BBRC) of Jiangsu Province, Suzhou, Jiangsu, China, to do the next #GUTBlog.

The #GUTBlog focusses on the paper entitled “Low-frequency repetitive transcranial magnetic stimulation attenuates visceral pain in IBS with diarrhoea via inhibition of the medial prefrontal cortex” which was published in paper copy in GUT in September 2026. Professors Li and Xu are the senior authors on this paper.

Professors Rui Li and Guang-Yin Xu write:

A patient’s question that started it all

It was a question we kept hearing in our outpatient department: “Doctor, why does it hurt so much when my gut looks normal?” For millions of people living with diarrhoea-predominant IBS (IBS-D), chronic abdominal pain is often the single biggest reason they cannot live a normal life. Yet existing treatments, antispasmodics, probiotics, often provide only temporary relief.

 

We became increasingly convinced that the answer to this question lies not in the gut alone, but in how the brain interprets and sometimes over-amplifies pain signals coming from the gut.

Finding the “volume dial” for gut pain

We started with a straightforward clinical observation. Using functional MRI (fMRI) in 21 IBS-D patients and 21 healthy volunteers, we searched for brain regions that were unusually active in patients with visceral pain. One region stood out: the medial prefrontal cortex (mPFC). The more active a patient’s mPFC was, the more severe their abdominal pain. This was our first clue, mPFC looked like a “volume dial” that turns up gut pain signals. But correlation isn’t causation. We need to know: is the mPFC actually causing the pain, or just responding to it?

What surprised us

We used a mouse model that mimics the IBS-D chronic visceral pain. Using real-time neuronal monitoring and control, we found that glutamatergic neurons in the mPFC drive visceral pain. Activating them induced gut pain in healthy mice, while inhibiting them eliminated the pain. Surprisingly, we traced this overactivity to a pathway from the anterior cingulate cortex (ACC) to the mPFC and identified a molecular player: a receptor subunit called NR2A, which was present at abnormally high levels in the mPFC of pain-model mice. Blocking NR2A relieved the pain. This level of detail, from brain region, to cell type, to neural circuit, to molecules, gave us confidence that the mPFC was a valid target for therapy.

Magnetic pulses to “turn down the dial”

If the mPFC was overactive, we reasoned that calming it down should relieve pain. We turned to low-frequency repetitive transcranial magnetic stimulation (lf-rTMS), a non-invasive technique already used in psychiatry, where magnetic pulses gently modulate brain activity through the scalp. In the mouse model, daily lf-rTMS sessions for two weeks not only relieve visceral pain but kept the pain threshold elevated for up to 42 days after treatment stopped. That durability surprised us.

Back to the clinic—would it work in humans?

 

We conducted a randomised, sham-controlled trial in 42 IBS-D patients. Half received real rTMS targeting the mPFC for two weeks; the other half received sham stimulation.

The results were encouraging:

• Patients in the real rTMS group reported significantly less visceral pain.
• Their rectal sensitivity improved: they could tolerate larger volumes during anorectal manometry.
• Their bowel habits became more regular, reflected by lower Bristol Stool Form Scale scores.
• And importantly, when we repeated the fMRI scans, we could see that mPFC activity had actually decreased in the treatment group.

In other words, we had literally “turned down the dial”.

How long does it last?

We followed patients for 8 weeks after treatment. Benefits held—pain scores remained lower, bowel habits stayed improved. That durability, combined with the fact that rTMS is non-invasive and well-tolerated, makes us optimistic about its potential as a long-term, non-drug option.

What this means—and what’s next

We presented this work at DDW 2025 in San Diego, and the response from colleagues was overwhelmingly positive. The most common question we heard was: “When can we start using this in our patients?” That’s exactly what we’re working on now. We are planning larger, multicentre trials to confirm these findings. We also want to explore whether this approach works in other IBS subtypes, and whether tailoring the stimulation site to each patient’s brain scan could make the treatment even more effective.

From a patient’s question to a lab discovery and back to the clinic, this study represents a complete translational loop. We started with a patient asking “why?” and ended with a potential new, non-drug option for people with IBS-D. Meanwhile, we have established a dedicated IBS outpatient service at our hospital, where we are now integrating these findings into clinical practice, aiming to offer rTMS as an adjunctive option for suitable patients. To us, that’s what research is all about.