Activation of the cholinergic antiinflammatory reflex by occipitoatlantal decompression and transcutaneous auricular vagus nerve stimulation

Context The parasympathetic-mediated inflammatory reflex inhibits excessive proinflammatory cytokine production. Noninvasive techniques, including occipitoatlantal decompression (OA-D) and transcutaneous auricular vagus nerve stimulation (taVNS), have been demonstrated to increase parasympathetic tone. Objectives To test the hypothesis that OA-D and taVNS increase parasympathetic nervous system activity and inhibit proinflammatory cytokine mobilization and/or production. Methods Healthy adult participants were randomized to receive OA-D (5 min of OA-D followed by 10 min of rest; n=8), taVNS (15 min; n=9), or no intervention (15 min, time control; n=10) on three consecutive days. Before and after these interventions, saliva samples were collected for determination of the cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor α (TNF-α). Arterial blood pressure and the electrocardiogram were recorded for a 30-min baseline, throughout the intervention, and during a 30-min recovery period to derive heart rate and blood pressure variability markers as indices of vagal and sympathetic control. Results OA-D and taVNS increased root mean square of successive RR interval differences (RMSSD) and high frequency heart rate variability, which are established markers for parasympathetic modulation of cardiac function. In all three groups, the experimental protocol was associated with a significant increase in salivary cytokine concentrations. However, the increase in IL-1β was significantly less in the taVNS group (+66 ± 13 pg/mL; p2 after OA-D vs. 28 ± 5 mmHg2 before OA-D; p Conclusions Both OA-D and taVNS elicited antiinflammatory responses that were associated with increases in heart rate variability-derived markers for parasympathetic function. These findings suggest that OA-D and taVNS activate the parasympathetic antiinflammatory reflex. Furthermore, an antihypertensive effect was observed with OA-D that may be mediated by reduced sympathetic modulation of vascular tone and/or increased baroreceptor reflex sensitivity.