The Role of the Vagus Nerve in Cancer Prognosis: A Systematic and a Comprehensive Review

This article reviews the role of the vagus nerve in tumor modulation and cancer prognosis. We present a systematic review of 12 epidemiological studies examining the relationship between heart rate variability, the main vagus nerve index, and prognosis in cancer patients (survival and tumor markers). These studies show that initially high vagal nerve activity predicts better cancer prognosis, and, in some studies, independent of confounders such as cancer stage and treatments. Since the design of the epidemiological studies is correlational, any causal relationship between heart rate variability and cancer prognosis cannot be inferred. However, various semi-experimental cohort studies in humans and experimental studies in animals have examined this causal relationship. The second part of this paper presents a comprehensive review including human and animal cohort and experimental studies showing that vagotomy accelerates tumor growth, while vagal nerve activation improves cancer prognosis. Based on all reviewed studies, it is concluded that the evidence supports a protective role of the vagus nerve in cancer and specifically in the metastatic stage.

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Motivational nondirective resonance breathing versus transcutaneous vagus nerve stimulation in the treatment of fibromyalgia: study protocol for a randomized controlled trial

Trials ◽

10.1186/s13063-020-04703-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Charles Ethan Paccione ◽

Lien My Diep ◽

Audun Stubhaug ◽

Henrik Børsting Jacobsen

Keyword(s):

Heart Rate ◽

Randomized Controlled Trial ◽

Heart Rate Variability ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Controlled Trial ◽

Vagal Nerve ◽

Randomized Controlled ◽

Transcutaneous Vagus Nerve Stimulation

Abstract Background Chronic widespread pain (CWP), including fibromyalgia (FM), affects one in every ten adults and is one of the leading causes of sick leave and emotional distress. Due to an unclear etiology and a complex pathophysiology, FM is a condition with few, if any, effective and safe treatments. However, current research within the field of vagal nerve innervation suggests psychophysiological and electrical means by which FM may be treated. This study will investigate the efficacy of two different noninvasive vagal nerve stimulation techniques for the treatment of FM. Methods The study will use a randomized, single-blind, sham-controlled design to investigate the treatment efficacy of motivational nondirective resonance breathing (MNRB™) and transcutaneous vagus nerve stimulation (Nemos® tVNS) on patients diagnosed with FM. Consenting FM patients (N = 112) who are referred to the Department of Pain Management and Research at Oslo University Hospital, in Oslo, Norway, will be randomized into one of four independent groups. Half of these participants (N = 56) will be randomized to either an experimental tVNS group or a sham tVNS group. The other half (N = 56) will be randomized to either an experimental MNRB group or a sham MNRB group. Both active and sham treatment interventions will be delivered twice per day at home, 15 min/morning and 15 min/evening, for a total duration of 2 weeks (14 days). Participants are invited to the clinic twice, once for pre- and once for post-intervention data collection. The primary outcome is changes in photoplethysmography-measured heart rate variability. Secondary outcomes include self-reported pain intensity on a numeric rating scale, changes in pain detection threshold, pain tolerance threshold, and pressure pain limit determined by computerized pressure cuff algometry, blood pressure, and health-related quality of life. Discussion The described randomized controlled trial aims to compare the efficacy of two vagal nerve innervation interventions, MNRB and tVNS, on heart rate variability and pain intensity in patients suffering from FM. This project tests a new and potentially effective means of treating a major public and global health concern where prevalence is high, disability is severe, and treatment options are limited. Trial registration ClinicalTrials.govNCT03180554. Registered on August 06, 2017.

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Motivational nondirective resonance breathing versus transcutaneous vagus nerve stimulation in the treatment of fibromyalgia: study protocol for a randomized controlled trial

10.21203/rs.3.rs-34040/v1 ◽

2020 ◽

Author(s):

Charles Ethan Paccione ◽

Lien My Diep ◽

Audun Stubhaug ◽

Henrik Børsting Jacobsen

Keyword(s):

Heart Rate ◽

Randomized Controlled Trial ◽

Heart Rate Variability ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Controlled Trial ◽

Vagal Nerve ◽

Randomized Controlled ◽

Transcutaneous Vagus Nerve Stimulation

Abstract BackgroundChronic widespread pain (CWP), including fibromyalgia (FM), affects one in every ten adults and is one of the leading causes of sick leave and emotional distress. Due to an unclear etiology and a complex pathophysiology, FM is a condition with few, if any, effective and safe treatments. However, current research within the field of vagal nerve innervation suggests psychophysiological and electrical means by which FM may be treated. This study will investigate the efficacy of two different non-invasive vagal nerve stimulation techniques for the treatment of FM.MethodsThe study will use a randomized, single blind, sham-controlled design to investigate the treatment efficacy of motivational nondirective resonance breathing (MNRBTM) and transcutaneous vagus nerve stimulation (Nemos® tVNS) on patients diagnosed with FM. Consenting FM patients (N=112) who are referred to the Department of Pain Management and Research at Oslo University Hospital, in Oslo, Norway, will be randomized into one of four independent groups. Half of these participants (N=56) will be randomized to either an experimental tVNS group or a sham tVNS group. The other half (N=56) will be randomized to either an experimental MNRB group or a sham MNRB group. Both active and sham treatment interventions will be delivered twice per day at home, 15 min/morning and 15 min/evening, for a total duration of 2 weeks (14 days). Participants are invited to the clinic twice, once for pre- and once for post-intervention data collection. The primary outcome is changes in photoplethysmography measured heart rate variability. Secondary outcomes include self-reported pain intensity on a numeric rating scale, changes in pain detection threshold, pain tolerance threshold, and pain-pressure limit determined by computerized pressure cuff algometry, blood pressure, and health related quality of life.DiscussionThe described randomized controlled trial aims to compare the efficacy of two vagal nerve innervation interventions, MNRB and tVNS, on heart rate variability and pain intensity in patients suffering from FM. This project tests a new and potentially effective means of treating a major public and global health concern where prevalence is high, disability is severe, and treatment options are limited.Trial registrationClinicalTrials.gov Identifier: NCT03180554; Date of Registration: 08/06/2017

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Decreased heart rate variability in transgenic mice overexpressing atrial beta 1-adrenoceptors

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.4.h1465 ◽

1996 ◽

Vol 271 (4) ◽

pp. H1465-H1472 ◽

Cited By ~ 21

Author(s):

P. Mansier ◽

C. Medigue ◽

N. Charlotte ◽

C. Vermeiren ◽

E. Coraboeuf ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Transgenic Mice ◽

Sinoatrial Node ◽

Experimental Studies ◽

Frequency Domain Analysis ◽

Node Density ◽

Time Frequency ◽

Respiratory Reflex

Heart rate variability (HRV) depends on various reflexes, including the baroreflex or respiratory reflex. Experimental studies have suggested that the sinoatrial node density in G protein-linked receptors may be involved. Transgenic mice, with a specific eightfold atrial overexpression of human beta 1-adrenoceptor (beta 1-AR), have been generated to evaluate the role of the atrial beta 1-AR density on HRV. The heart rate was monitored using telemetry, and the signal was analyzed using a quantitative time-frequency domain analysis, the smoothed pseudo-Wigner-Ville method, and phase portrait maps. 1) Heart rate was unchanged, but the two normal components of HRV were decreased in transgenic mice. Transgenic mice have an unshortened life span and no arrhythmias. 2) Challenge of the animals by propranolol showed no modulation of the HRV in transgenic mice compared with controls. 3) In isolated atrial strips from transgenic mice, basal contractility was increased and there was no isoproterenol-induced inotropic effect. 4) The basal level of adenosine 3',5'-cyclic monophosphate production was lowered in transgenic mice, suggesting a shift in adenylate cyclase isoforms.

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