Abdominal ultrasound activates afferent vagus nerve fibers and induces anti-inflammatory effects
Kotaro Shimoyama, Mamoru Tanida, Jun Aruga, Tomohiro Furusato, Chia-Hsien Wu, Yasuna Nakamura, Daisuke Takahashi, Go Kanzaki, Atsuhiro Maeda, Takao Shioya, Nobuo Tsuboi, Chikara Abe, Takashi Yokoo, Ryusuke Umene, Tsuyoshi Inoue
Proceedings of the National Academy of Sciences 2026, 123 · 10.1073/pnas.2518969123
Abstract
Abdominal ultrasound has emerged as a noninvasive modality with immunomodulatory potential. Although its anti-inflammatory effects have been demonstrated in various disease models, the underlying mechanisms remain unclear. Previous studies suggest that ultrasound promotes anti-inflammatory macrophage polarization via α7 nicotinic acetylcholine receptor (α7nAChR) signaling in the spleen. However, the upstream events initiating this response have not been elucidated. Here, we demonstrate that abdominal ultrasound activates afferent vagal fibers and suppress systemic inflammation. In a murine model of lipopolysaccharide (LPS)-induced endotoxemia, abdominal ultrasound significantly reduced plasma TNF-α levels. This anti-inflammatory effect was attenuated by subdiaphragmatic vagotomy (SDVx) or afferent vagal blockade. Electrophysiological recordings revealed increased cervical vagus nerve activity during ultrasound stimulation, which was eliminated by intraperitoneal lidocaine, confirming activation of abdominal sensory afferents. Furthermore, abdominal ultrasound induced c-Fos expression in the nucleus tractus solitarius (NTS), consistent with central activation via vagal afferent input. These findings provide direct mechanistic evidence that abdominal ultrasound stimulates afferent vagal pathways.
Abstract via europepmc.
Exposures
Exposure 1: Abdominal ultrasound stimulation (activating vagal afferents)
Target: vagus nerve — “abdominal ultrasound activating afferent vagus nerve fibers”
Device: not reported
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 14,000 | ✓✓✓⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 600 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
C57BL/6J mice were subjected to 10 min of abdominal ultrasound stimulation (Burst Mode, 14 MHz), followed by intraperitoneal injection of LPS (15 mg/kg), and then an additional 10 min of ultrasound stimulation. Detailed experimental methods (including full parameters and animal numbers) are provided in the SI Appendix, which was not available for extraction.
Flags from extraction
exposures[0].fundamental_frequency_khz— 14 MHz is a diagnostic-imaging-range frequency, unusually high compared with typical TUS neuromodulation studies (hundreds of kHz to low MHz); verify this is not a typo.exposures[0].timing.waveform— the paper only states the device setting 'Burst Mode' without giving pulse duration, PRF, or duty cycle, so the underlying pulsing scheme is unknown; classified as pulsed based on the device mode name alone.exposures[0].target.terms— the exact sonicated anatomical site (e.g., spleen vs. general abdomen) is not explicitly stated in the main text; target chosen based on the paper's framing that abdominal ultrasound activates afferent vagus nerve fibers.n_subjects— experimental methods, including animal group sizes, are stated to be in the SI Appendix, which was not available for extraction; main text gives no numeric N.exposures[0].device.family— no device manufacturer or model is given in the main text (methods are in SI Appendix).