{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:30:43Z","timestamp":1790767843985,"version":"4.1.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T00:00:00Z","timestamp":1614297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004836","name":"Det Frie Forskningsr\u00e5d","doi-asserted-by":"publisher","award":["DFF \u2013 7016-00073"],"award-info":[{"award-number":["DFF \u2013 7016-00073"]}],"id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010727","name":"Axel Muusfeldts Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010727","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008269","name":"L\u00e6ge Sophus Carl Emil Friis og hustru Olga Doris Friis' Legat","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\"><jats:title>Background &amp; aims<\/jats:title><jats:p>Chronic abdominal pain is the primary symptom of chronic pancreatitis, but unfortunately it is difficult to treat. Vagal nerve stimulation studies have provided evidence of anti-nociceptive effect in several chronic pain conditions. We investigated the pain-relieving effects of transcutaneous vagal nerve stimulation in comparison to sham treatment in chronic pancreatitis patients.<\/jats:p><\/jats:sec><jats:sec id=\"sec002\"><jats:title>Methods<\/jats:title><jats:p>We conducted a randomised double-blinded, sham-controlled, crossover trial in patients with chronic pancreatitis. Patients were randomly assigned to receive a two-week period of cervical transcutaneous vagal nerve stimulation using the gammaCore device followed by a two-week sham stimulation, or vice versa. We measured clinical and experimental endpoints before and after each treatment. The primary clinical endpoint was pain relief, documented in a pain diary using a visual analogue scale. Secondary clinical endpoints included Patients\u2019 Global Impression of Change score, quality of life and Brief Pain Inventory questionnaire. Secondary experimental endpoints included cardiac vagal tone and heart rate.<\/jats:p><\/jats:sec><jats:sec id=\"sec003\"><jats:title>Results<\/jats:title><jats:p>No differences in pain scores were seen in response to two weeks transcutaneous vagal nerve stimulation as compared to sham treatment (difference in average pain score (visual analogue scale): 0.17, 95%CI (-0.86;1.20), P = 0.7). Similarly, no differences were seen for secondary clinical endpoints, except from an increase in the appetite loss score (13.9, 95%CI (0.5:27.3), P = 0.04). However, improvements in maximum pain scores were seen for transcutaneous vagal nerve stimulation and sham treatments as compared to their respective baselines: vagal nerve stimulation (-1.3\u00b11.7, 95%CI (-2.21:-0.42), P = 0.007), sham (-1.3\u00b11.9, 95%CI (-2.28:-0.25), P = 0.018). Finally, heart rate was decreased after two weeks transcutaneous vagal nerve stimulation in comparison to sham treatment (-3.7 beats\/min, 95%CI (-6.7:-0.6), P = 0.02).<\/jats:p><\/jats:sec><jats:sec id=\"sec004\"><jats:title>Conclusion<\/jats:title><jats:p>In this sham-controlled crossover study, we found no evidence that two weeks transcutaneous vagal nerve stimulation induces pain relief in patients with chronic pancreatitis.<\/jats:p><\/jats:sec><jats:sec id=\"sec005\"><jats:title>Trial registration number<\/jats:title><jats:p>The study is registered at<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03357029\" xlink:type=\"simple\">NCT03357029<\/jats:ext-link>;<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\" xlink:type=\"simple\">www.clinicaltrials.gov<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1371\/journal.pone.0247653","type":"journal-article","created":{"date-parts":[[2021,2,26]],"date-time":"2021-02-26T18:39:38Z","timestamp":1614364778000},"page":"e0247653","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Cervical transcutaneous vagal neuromodulation in chronic pancreatitis patients with chronic pain: A randomised sham controlled clinical trial"],"prefix":"10.1371","volume":"16","author":[{"given":"Janusiya Anajan","family":"Muthulingam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren Schou","family":"Olesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine Maria","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Brock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asbj\u00f8rn Mohr","family":"Drewes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8722-0070","authenticated-orcid":true,"given":"Jens Br\u00f8ndum","family":"Fr\u00f8kj\u00e6r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,2,26]]},"reference":[{"key":"pone.0247653.ref001","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1001\/jama.2019.19411","article-title":"Diagnosis and Management of Chronic Pancreatitis: A Review","volume":"322","author":"VK 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