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Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal

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 effect...

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Autores principales: Gazi, Asim H., Harrison, Anna B., Lambert, Tamara P., Nawar, Afra, Obideen, Malik, Driggers, Emily G., Vaccarino, Viola, Shah, Amit J., Rozell, Christopher J., Bikson, Marom, Welsh, Justine W., Inan, Omer T., Bremner, J. Douglas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682166/
https://www.ncbi.nlm.nih.gov/pubmed/36438447
http://dx.doi.org/10.3389/fpain.2022.1031368
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author Gazi, Asim H.
Harrison, Anna B.
Lambert, Tamara P.
Nawar, Afra
Obideen, Malik
Driggers, Emily G.
Vaccarino, Viola
Shah, Amit J.
Rozell, Christopher J.
Bikson, Marom
Welsh, Justine W.
Inan, Omer T.
Bremner, J. Douglas
author_facet Gazi, Asim H.
Harrison, Anna B.
Lambert, Tamara P.
Nawar, Afra
Obideen, Malik
Driggers, Emily G.
Vaccarino, Viola
Shah, Amit J.
Rozell, Christopher J.
Bikson, Marom
Welsh, Justine W.
Inan, Omer T.
Bremner, J. Douglas
author_sort Gazi, Asim H.
collection PubMed
description 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 (n = 9) or sham stimulation (n = 11) throughout the protocol. At the beginning and end of the protocol, patients' pain levels were assessed using the numerical rating scale (0–10 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 Δ) were computed for all measures. Δ NRS Pain scores were lower (P = 0.045) for the active group (mean ± standard deviation: −0.8 ± 2.4) compared to the sham group (0.9 ± 1.0). A positive correlation existed between Δ NRS pain scores and Δ RPV (Spearman's ρ = 0.46; P = 0.04). Following adjustment for device group, a negative correlation existed between Δ HRV and Δ NRS Pain (Spearman's ρ = −0.43; P = 0.04). 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.
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spelling pubmed-96821662022-11-24 Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal Gazi, Asim H. Harrison, Anna B. Lambert, Tamara P. Nawar, Afra Obideen, Malik Driggers, Emily G. Vaccarino, Viola Shah, Amit J. Rozell, Christopher J. Bikson, Marom Welsh, Justine W. Inan, Omer T. Bremner, J. Douglas Front Pain Res (Lausanne) Pain Research 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 (n = 9) or sham stimulation (n = 11) throughout the protocol. At the beginning and end of the protocol, patients' pain levels were assessed using the numerical rating scale (0–10 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 Δ) were computed for all measures. Δ NRS Pain scores were lower (P = 0.045) for the active group (mean ± standard deviation: −0.8 ± 2.4) compared to the sham group (0.9 ± 1.0). A positive correlation existed between Δ NRS pain scores and Δ RPV (Spearman's ρ = 0.46; P = 0.04). Following adjustment for device group, a negative correlation existed between Δ HRV and Δ NRS Pain (Spearman's ρ = −0.43; P = 0.04). 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. Frontiers Media S.A. 2022-11-09 /pmc/articles/PMC9682166/ /pubmed/36438447 http://dx.doi.org/10.3389/fpain.2022.1031368 Text en © 2022 Gazi, Harrison, Lambert, Nawar, Obideen, Driggers, Vaccarino, Shah, Rozell, Bikson, Welsh, Inan and Bremner. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) (https://creativecommons.org/licenses/by/4.0/) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pain Research
Gazi, Asim H.
Harrison, Anna B.
Lambert, Tamara P.
Nawar, Afra
Obideen, Malik
Driggers, Emily G.
Vaccarino, Viola
Shah, Amit J.
Rozell, Christopher J.
Bikson, Marom
Welsh, Justine W.
Inan, Omer T.
Bremner, J. Douglas
Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
title Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
title_full Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
title_fullStr Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
title_full_unstemmed Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
title_short Pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
title_sort pain is reduced by transcutaneous cervical vagus nerve stimulation and correlated with cardiorespiratory variability measures in the context of opioid withdrawal
topic Pain Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682166/
https://www.ncbi.nlm.nih.gov/pubmed/36438447
http://dx.doi.org/10.3389/fpain.2022.1031368
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