Lf-rTMS Attenuates Visceral Pain in Irritable Bowel Syndrome With Diarrhea

Low-frequency Repetitive Transcranial Magnetic Stimulation Attenuates Visceral Pain in Irritable Bowel Syndrome With Diarrhea Via Inhibition of the Medial Prefrontal Cortex

Objectives: To identify a central hub of visceral pain in IBS-D and elucidate the mechanism by which repetitive transcranial magnetic stimulation (rTMS) confers analgesic effects.

Methods: A total of 42 IBS-D patients were recruited and randomly assigned (1:1) to the sham rTMS or the rTMS group. A nested cohort of 21 IBS-D participants who completed baseline fMRI assessments prior to randomization was included. Consistent with the randomization procedure，these individuals were evenly distributed between the two groups. Both participants and outcome assessors remained blinded to treatment allocation throughout the study. All patients completed the two-week intervention and were included in the final analysis.

Background：Chronic visceral pain in irritable bowel syndrome with diarrhea (IBS-D) is a profound therapeutic challenge. While aberrant central processing is implicated, the key brain regions driving this visceral pain and their suitability as neuromodulatory targets remain undefined.

Methods: Participants were randomly assigned (1:1) to the sham rTMS or rTMS group using a computer-generated randomization sequence created by an independent researcher who was not involved in recruitment, treatment, or outcome assessment. Allocation concealment was ensured using sequentially numbered, opaque, sealed envelopes, which were opened only after baseline evaluations were completed.

Both participants and outcome assessors were blinded to treatment allocation. The rTMS operators were not involved in data collection or analysis. For the sham condition, the coil was positioned identically over the mPFC with magnetic output disabled, and prerecorded clicking sounds were delivered to mimic the acoustic sensation of stimulation. Participants were asked not to discuss treatment sensations with assessors. Scale raters and fMRI analysts remained blinded until all analyses were finalized.

For the nested fMRI cohort, randomization and blinding procedures were identical, with group allocation revealed only after preprocessing and statistical analysis had been completed.

All diagnoses were made by board-certified gastroenterologists. Eligible participants met the following inclusion criteria: (1) age between 18 and 75 years; (2) fulfillment of the Rome IV diagnostic criteria for IBS-D. Exclusion criteria included: (1) presence of inflammatory or other organic gastrointestinal diseases; (2) diagnosed psychiatric disorders; (3) history of anorectal, intestinal, or abdominal surgery; (4) pregnancy or lactation; (5) presence of metallic implants or cardiac pacemakers.