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


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Randomized Controlled Trial, Clinical trial


Osteopathic Manipulative Treatment

J Osteopath Med. 2021 Feb 24;121(4):401-415.


Adrienne M Kania, Kailee N Weiler, Angeline P Kurian, Marielle L Opena, Jennifer N Orellana, Harald M Stauss


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; p<0.05) than in the time control group (+142 ± 24 pg/mL). A similar trend was observed in the taVNS group for TNF-α (+1.7 ± 0.3 pg/mL vs. 4.1 ± 1.3 pg/mL; p<0.10). In the OA-D group baseline IL-6, IL-8, and TNF-α levels on the third study day were significantly lower than on the first study day (IL-6: 2.3 ± 0.4 vs. 3.2 ± 0.6 pg/mL, p<0.05; IL-8: 190 ± 61 vs. 483 ± 125 pg/mL, p <0.05; TNF-α: 1.2 ± 0.3 vs. 2.3 ± 0.4 pg/mL, p<0.05). OA-D decreased mean blood pressure from the first (100 ± 8 mmHg) to the second (92 ± 6 mmHg; p<0.05) and third (93 ± 8 mmHg; p<0.05) study days and reduced low frequency spectral power of systolic blood pressure variability (19 ± 3 mmHg2 after OA-D vs. 28 ± 5 mmHg2 before OA-D; p<0.05), a marker of sympathetic modulation of vascular tone. OA-D also increased baroreceptor-heart rate reflex sensitivity from the first (13.7 ± 3.0 ms/mmHg) to the second (18.4 ± 4.3 ms/mmHg; p<0.05) and third (16.9 ± 4.2 ms/mmHg; p<0.05) study days.

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.

Publication Date: 

2021 Feb



Kania, MA., Weiler, NK., Kurian, PA., Opena, LM., Orellana, NJ., Stauss, MH. (2021) 'Activation of the cholinergic antiinflammatory reflex by occipitoatlantal decompression and transcutaneous auricular vagus nerve stimulation ', J Osteopath Med. 2021 Feb 24;121(4):401-415.

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