{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T02:53:08Z","timestamp":1784170388891,"version":"3.55.0"},"reference-count":62,"publisher":"Walter de Gruyter GmbH","issue":"4","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Research Office of Burrell College of Osteopathic Medicine"},{"DOI":"10.13039\/100002594","name":"American Osteopathic Association","doi-asserted-by":"crossref","award":["19137759"],"award-info":[{"award-number":["19137759"]}],"id":[{"id":"10.13039\/100002594","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jom-2020-0071_abs_001_w2aab3b7c15b1b6b1aab1c16b1Aa\">\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2020-0071_abs_002_w2aab3b7c15b1b6b1aab1c16b2Aa\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To test the hypothesis that OA-D and taVNS increase parasympathetic nervous system activity and inhibit proinflammatory cytokine mobilization and\/or production.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2020-0071_abs_003_w2aab3b7c15b1b6b1aab1c16b3Aa\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Healthy adult participants were randomized to receive OA-D (5\u00a0min of OA-D followed by 10\u00a0min of rest; n=8), taVNS (15\u00a0min; n=9), or no intervention (15\u00a0min, time control; n=10) on three consecutive days. Before and after these interventions, saliva samples were collected for determination of the cytokines interleukin-1\u03b2 (IL-1\u03b2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor \u03b1 (TNF-\u03b1). 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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2020-0071_abs_004_w2aab3b7c15b1b6b1aab1c16b4Aa\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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-1\u03b2 was significantly less in the taVNS group (+66\u00a0\u00b1\u00a013\u00a0pg\/mL; p&lt;0.05) than in the time control group (+142\u00a0\u00b1\u00a024\u00a0pg\/mL). A similar trend was observed in the taVNS group for TNF-\u03b1 (+1.7\u00a0\u00b1\u00a00.3\u00a0pg\/mL vs. 4.1\u00a0\u00b1\u00a01.3\u00a0pg\/mL; p&lt;0.10). In the OA-D group baseline IL-6, IL-8, and TNF-\u03b1 levels on the third study day were significantly lower than on the first study day (IL-6: 2.3\u00a0\u00b1\u00a00.4 vs. 3.2\u00a0\u00b1\u00a00.6\u00a0pg\/mL, p&lt;0.05; IL-8: 190\u00a0\u00b1\u00a061 vs. 483\u00a0\u00b1\u00a0125\u00a0pg\/mL, p &lt;0.05; TNF-\u03b1: 1.2\u00a0\u00b1\u00a00.3 vs. 2.3\u00a0\u00b1\u00a00.4\u00a0pg\/mL, p&lt;0.05). OA-D decreased mean blood pressure from the first (100\u00a0\u00b1\u00a08\u00a0mmHg) to the second (92\u00a0\u00b1\u00a06\u00a0mmHg; p&lt;0.05) and third (93\u00a0\u00b1\u00a08\u00a0mmHg; p&lt;0.05) study days and reduced low frequency spectral power of systolic blood pressure variability (19\u00a0\u00b1\u00a03\u00a0mmHg<jats:sup>2<\/jats:sup> after OA-D vs. 28\u00a0\u00b1\u00a05\u00a0mmHg<jats:sup>2<\/jats:sup> before OA-D; p&lt;0.05), a marker of sympathetic modulation of vascular tone. OA-D also increased baroreceptor-heart rate reflex sensitivity from the first (13.7\u00a0\u00b1\u00a03.0\u00a0ms\/mmHg) to the second (18.4\u00a0\u00b1\u00a04.3\u00a0ms\/mmHg; p&lt;0.05) and third (16.9\u00a0\u00b1\u00a04.2\u00a0ms\/mmHg; p&lt;0.05) study days.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jom-2020-0071_abs_005_w2aab3b7c15b1b6b1aab1c16b5Aa\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jom-2020-0071","type":"journal-article","created":{"date-parts":[[2021,2,28]],"date-time":"2021-02-28T04:31:18Z","timestamp":1614486678000},"page":"401-415","source":"Crossref","is-referenced-by-count":21,"title":["Activation of the cholinergic antiinflammatory reflex by occipitoatlantal decompression and transcutaneous auricular vagus nerve stimulation"],"prefix":"10.1515","volume":"121","author":[{"given":"Adrienne M.","family":"Kania","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine , Burrell College of Osteopathic Medicine , Las Cruces , NM , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailee N.","family":"Weiler","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine , Burrell College of Osteopathic Medicine , Las Cruces , NM , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angeline P.","family":"Kurian","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine , Burrell College of Osteopathic Medicine , Las Cruces , NM , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle L.","family":"Opena","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine , Burrell College of Osteopathic Medicine , Las Cruces , NM , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer N.","family":"Orellana","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine , Burrell College of Osteopathic Medicine , Las Cruces , NM , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald M.","family":"Stauss","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences , Burrell College of Osteopathic Medicine , Las Cruces , NM , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"2023040101100651932_j_jom-2020-0071_ref_001_w2aab3b7c15b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Strand, V, Kimberly, R, Isaacs, JD. 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