Anti‐inflammatory Effect of Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation and Osteopathic Manipulative Treatment
Authors: Stauss Harald M. , Kurian Angeline P. , Orellana Jennifer N. , Weiler Kailee N. , Whitson Deborah D.S. , Kania Adrienne M. 
Published: April 2020

BackgroundThe anti‐inflammatory reflex inhibits excessive pro‐inflammatory cytokine production through the parasympathetic nervous system. It has been demonstrated that non‐invasive transcutaneous auricular vagus nerve stimulation (taVNS) increases various heart rate variability (HRV)‐derived parameters that are associated with parasympathetic modulation of cardiac function. Likewise, osteopathic occipito‐atlantal decompression (OA‐D) has been demonstrated to increase HRV, consistent with increased vagal tone. However, it is not known if these interventions also inhibit inflammation. Thus, the hypothesis of this study was that noninvasive taVNS and osteopathic OA‐D decrease synthesis and/or release of pro‐inflammatory cytokines through an increase in parasympathetic nervous system activity.MethodsAdult healthy participants received OA‐D (5 min, n=7), taVNS (15 min, n=8), or no intervention (15 min, control group, n=8) on three consecutive days. Before and after these interventions, noninvasive arterial blood pressure (Finapres Finometer Pro) and the ECG were recorded continuously for 30 min. Before and after each daily experiment, saliva samples were collected for determination of salivary interleukin‐1β (IL‐1β) and tumor necrosis factor α (TNF‐α) by ELISA.ResultsOnly in the OA‐D group, mean blood pressure decreased from the first (100±8 mmHg) to the third (93±8 mmHg, P<0.05) study day. Low frequency blood pressure variability, a marker of sympathetic modulation of vascular tone, declined only in response to OA‐D (− 8.6±3.5 mmHg2, P<0.05 vs. +3.8±2.9 mmHg2 in taVNS and +1.0±2.9 mmHg2 in control). RMSSD, a time domain HRV parameter that reflects parasympathetic modulation of cardiac function, increased only in response to taVNS (+5.0±1.6 ms, P<0.05 vs. +2.4±4.8 ms in OA‐D and +3.1±3.8 ms in control). In control subjects the 2‐hour experimental procedure increased salivary IL‐1β (+288±84 pg/mL, P<0.05) and TNF‐α (+2.5±0.3 pg/mL, P<0.05). As illustrated in Fig.
1, noninvasive taVNS blunted both, the IL‐1β (+54±18 pg/mL, P<0.05 vs. control) and TNF‐α (+1.5±0.3 pg/mL, P<0.05 vs. control) responses, while OA‐D reduced only the IL‐1β response (+104±43 pg/mL, P<0.05 vs. control).Summary/ConclusionOA‐D reduces arterial blood pressure, possibly through inhibition of sympathetic modulation of vascular function. The experimental protocol was associated with a pro‐inflammatory response as indicated by the marked increase in salivary IL‐1β and TNF‐α in the control group. This pro‐inflammatory response was inhibited by OA‐D and taVNS, although this anti‐inflammatory effect was more pronounced by taVNS that blunted both, the IL‐1β and TNF‐α responses, while OA‐D only reduced the IL‐1β response. The increase in RMSSD associated with taVNS suggests that taVNS inhibits inflammation through the parasympathetic anti‐inflammatory reflex.Support or Funding InformationSupported by the American Osteopathic Association (Grant #19137759) and generous funding by the Research Office at Burrell College of Osteopathic Medicine.Differences (⊗) in the salivary concentrations of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β, left) and tumor necrosis factor‐α (TNF‐α, right) before and after the experimental protocol. The cytokine concentrations from days 1 to 3 were averaged. CTR: control group; OMT: osteopathic occipito‐atlantal decompression (OA‐D) group; taVNS: transcutaneous auricular vagus nerve stimulation group; *: P<0.05 vs control.Figure 1