SPARC: Transcutaneous Auricular Vagal Nerve Stimulation Increases Antroduodenal Motility in Rat within a Narrow Range of Stimulus Parameters

Abstract

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising, non‐invasive approach to modulate activity in the central nervous system, heart, lungs, stomach and other organs that receive projections from the vagus nerve. The optimal stimulus parameters for modulating stomach function are unknown, preventing further development of taVNS as a device‐based treatment for motility disorders like gastroparesis. We hypothesized that taVNS parameters could be tuned to preferentially modulate antroduodenal motility with fewer off‐target effects on the heart than cervical VNS. Using a custom‐made stimulation and recording system (Autonomous Neural Control, or ANC), we surveyed the taVNS‐mediated effects on cardiac, vagal (ventral gastric branch), antral and duodenal motility in male Sprague Dawley rats under isoflurane anesthesia (250–400 g; N = 14 rats). With custom carbon gel electrodes, we stimulated the left cymba concha at 1 or 10 Hz using 28 combinations of stimulus pulse currents and durations (0, 0.2, 0.4, 0.6, 0.8, 1.0 and 1.2 mA pulse currents in combination with 0.1, 0.2, 0.4 and 0.8 ms pulse durations), while measuring the electrocardiogram, antral electrogastrogram, and antral/duodenal motility with implanted strain gauges. The ANC software applied each stimulus parameter combination in a random order in 60 s cycles (20 s ON/40 s OFF). Stimulus pulse durations less than 0.4 ms were not associated with any significant effects on cardiac (measured from the electrocardiogram) or gastric activity (measured from the antral electrogastrogram as well as antral and duodenal strain gauge recordings), but did produce notable increases in nerve activity at the level of the ventral gastric branch (measured with an implanted bipolar cuff electrode). A pulse duration of 0.8 ms produced the most robust and consistent decrease in heart rate, increase in heart rate variability, increase in antral smooth muscle activity, and increase in antroduodenal motility, as is expected from an increase in vagal outflow. In contrast to cervical VNS, where the optimal parameters for increasing antral motility largely overlapped with those that induced severe bradycardia, the optimal taVNS parameters that increased antroduodenal motility at 1 or 10 Hz (Pulse Current: 0.2–0.6 mA | Pulse Duration: 0.4–0.8 ms) required less current, on average, than the stimulus parameters that produced the greatest reduction in heart rate and increase in heart rate variability (Pulse Current: 0.4–1.0 mA | Pulse Duration: 0.4–0.8 ms). Pulse currents greater than 0.6 mA did not have any significant effect on antroduodenal motility, supporting the value of our parameter search approach in sorting the useful from the useless stimulus parameters. These results strongly support taVNS as a viable approach to modulate gastrointestinal activity with greater specificity and control over stomach function than cervical VNS.Support or Funding InformationThis work was supported by NIH SPARC OT2 OD023847