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Pain Res."],"abstract":"<jats:p>Over 100,000 individuals in the United States lost their lives secondary to drug overdose in 2021, with opioid use disorder (OUD) being a leading cause. Pain is an important component of opioid withdrawal, which can complicate recovery from OUD. This study's objectives were to assess the effects of transcutaneous cervical vagus nerve stimulation (tcVNS), a technique shown to reduce sympathetic arousal in other populations, on pain during acute opioid withdrawal and to study pain's relationships with objective cardiorespiratory markers. Twenty patients with OUD underwent opioid withdrawal while participating in a two-hour protocol. The protocol involved opioid cues to induce opioid craving and neutral conditions for control purposes. Adhering to a double-blind design, patients were randomly assigned to receive active tcVNS (<jats:italic>n<\/jats:italic>\u2009=\u20099) or sham stimulation (<jats:italic>n<\/jats:italic>\u2009=\u200911) throughout the protocol. At the beginning and end of the protocol, patients' pain levels were assessed using the numerical rating scale (0\u201310 scale) for pain (NRS Pain). During the protocol, electrocardiogram and respiratory effort signals were measured, from which heart rate variability (HRV) and respiration pattern variability (RPV) were extracted. Pre- to post- changes (denoted with a \u0394) were computed for all measures. \u0394 NRS Pain scores were lower (<jats:italic>P<\/jats:italic>\u2009=\u20090.045) for the active group (mean\u2009\u00b1\u2009standard deviation: \u22120.8\u2009\u00b1\u20092.4) compared to the sham group (0.9\u2009\u00b1\u20091.0). A positive correlation existed between \u0394 NRS pain scores and \u0394 RPV (Spearman's <jats:italic>\u03c1<\/jats:italic>\u2009=\u20090.46; <jats:italic>P<\/jats:italic>\u2009=\u20090.04). Following adjustment for device group, a negative correlation existed between \u0394 HRV and \u0394 NRS Pain (Spearman's <jats:italic>\u03c1<\/jats:italic>\u2009=\u2009\u22120.43; <jats:italic>P<\/jats:italic>\u2009=\u20090.04). This randomized, double-blind, sham-controlled pilot study provides the first evidence of tcVNS-induced reductions in pain in patients with OUD experiencing opioid withdrawal. This study also provides the first quantitative evidence of an association between breathing irregularity and pain. The correlations between changes in pain and changes in objective physiological markers add validity to the data. Given the clinical importance of reducing pain non-pharmacologically, the findings support the need for further investigation of tcVNS and wearable cardiorespiratory sensing for pain monitoring and management in patients with OUD.<\/jats:p>","DOI":"10.3389\/fpain.2022.1031368","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T07:45:02Z","timestamp":1667979902000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal"],"prefix":"10.3389","volume":"3","author":[{"given":"Asim H.","family":"Gazi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna B.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara P.","family":"Lambert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afra","family":"Nawar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malik","family":"Obideen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily G.","family":"Driggers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Vaccarino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit J.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Rozell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marom","family":"Bikson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine W.","family":"Welsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omer T.","family":"Inan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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