In vivo evaluation of noninvasive temporal interference stimulation for tibial nerve-mediated bladder reflex modulation in rats

Transcutaneous tibial nerve stimulation (TTNS) is an established noninvasive neuromodulation approach for modulating bladder reflexes, although neural recruitment may vary with electrode configuration and tissue electrical properties. Temporal interference stimulation (TIS) is an emerging neuromodulation approach in which interacting kilohertz-frequency currents produce low-frequency amplitude modulation and may provide an alternative strategy for peripheral nerve stimulation. We investigated bladder reflex changes following noninvasive TIS applied over the intended tibial nerve region and explored its intensity-response pattern relative to conventional TTNS.

In the primary experiment, rats were randomized to TIS or TTNS, and each rat was tested at five motor threshold (MT)-normalized intensity levels in a repeated-measures protocol. Cystometry assessed first voiding time (VT), intercontraction interval (ICI), and bladder pressure before and after each stimulation block. TIS showed the largest mean changes at 100% MT, with prolonged VT and ICI and reduced bladder pressure relative to baseline.

Exploratory between-modality comparisons suggested different MT-normalized intensity-response patterns, with the largest VT and ICI differences at 100% MT; differences at other matched intensities were not significant. No significant between-modality bladder-pressure differences were detected. These findings provide a preliminary characterization of peripheral TIS intensity-response patterns for bladder reflex modulation and support further evaluation in disease-relevant models.

We would like to acknowledge our dedicated research assistants from Prof. Chih-Wei Peng’s Lab and the technical support of the Animal Center at Taipei Medical University. The present study was generously funded by the National Science and Technology Council (112-2221-E-038-004-MY3, 113-2622-E-038 -008, 114-2811-E-038 -003, and 114-2622-E-038 -003), and the Higher Education Sprout Project (DP2-TMU-115-N-01) of the Ministry of Education (MOE), the TMU/CWRU (CTSC) Pilot Program (113-6833-002-400), and the University System of Taipei Joint Research Program (USTP-NTPU-TMU-113-01) in Taiwan.

Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan Department of Physical Therapy, Faculty of Health Science, University of Muhammadiyah Malang, Malang, Indonesia Department of Computer Science and Information Engineering, National Taipei University, New Taipei, Taiwan Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei, Taiwan Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Departments of Biomedical Engineering & Urology, Case Western Reserve University, Cleveland, OH, USA School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan Division of Neurosurgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan Chun-Wei Wu, Jian-Chiun Liou & Chih-Wei Peng Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Department of Physical Medicine and Rehabilitation, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Below is the link to the electronic supplementary material.

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