Validation and Reliability of a Novel Vagus Nerve Neurodynamic Test and Its Effects on Heart Rate in Healthy Subjects: Little Differences Between Sexes

Giacomo Carta, Agnese Seregni, Andrea Casamassima, Manuela Galli, Stefano Geuna, Pasquale Pagliaro, Matteo Zago, Giacomo Carta, Agnese Seregni, Andrea Casamassima, Manuela Galli, Stefano Geuna, Pasquale Pagliaro, Matteo Zago

Abstract

Background: The vagus nerve (VN), also called the pneumogastric nerve, connects the brainstem to organs contained in the chest and abdomen. Physiologically, VN stimulation can rapidly affect cardiac activity and heart rate (HR). VN neuropathy can increase the risk of arrhythmias and sudden death. Therefore, a selective test of VN function may be very useful. Since peripheral neurodynamic tests (NDT) are reliable for the assessment of neuropathies in somatic nerves, we aimed to validate a novel NDT to assess VN activity, namely, the VN-NTD.

Methods: In this cross-sectional double-blind, sex-balanced study, 30 participants (15 females) completed a checklist of autonomic dysfunction symptoms. During the VN-NDT administration, HR and symptoms (i.e., mechanical allodynia) were monitored in parallel to a real-time ultrasonography imaging (USI) and motion capture analysis of the neck. The VN-NDT impact on HR and its accuracy for autonomic symptoms reported in the last 7 days were tested.

Results: The VN-NDT induced a significant HR reduction of about 12 and 8 bpm in males and females [t(1, 119) = 2.425; p < 0.017; ηp 2 = 0.047, 95% confidence interval (CI): 0.93-9.18], respectively. No adverse events were observed during VN-NDT. A substantial interexaminer agreement between the evaluators in symptoms induction by VN-NDT was detected [F(1, 119) = 0.540; p = 0.464; ηp 2 = 0.005, low effect]. Notably, mechanical allodynia accuracy for gastrointestinal dysfunctions was excellent (p < 0.05; 95% CI: 0.52-0.73; p < 0.001; 95% CI: 0.81-0.96).

Conclusions: The novel VN-NDT is a valid and accurate test capable of detecting VN activation with high sensitivity. Data provided are suitable for both sexes as a hallmark of HR variation due to VN normal response. The proposed VN-NDT may be reliable as daily routine neurological examination tests for the evaluation of neuropathic signs related to neuroinflammation of the VN.

Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04192877.

Keywords: diagnostic test; heart rate; neuropathic pain; ultrasound; vagus nerve stimulation.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Carta, Seregni, Casamassima, Galli, Geuna, Pagliaro and Zago.

Figures

FIGURE 1
FIGURE 1
Sequence of the vagus nerve neurodynamic test (VN-NDT) with (1) starting position with upper cervical spine in flexion. (2) Contralateral lateral flexion. (3) Ipsilateral neck rotation. (4) The end position of the test with gentle movements of the upper abdomen caudally and cranially as discrimination maneuverers.
FIGURE 2
FIGURE 2
STARD flowchart of the vagus nerve neurodynamic test (VN-NDT).
FIGURE 3
FIGURE 3
(A) Effect of the VN-NDT on HR in males and females. Values in the graph are expressed as mean ± SD. Two-way ANOVA was carried out (data are normally distributed with comparable variances); asterisk shows the statistically significant difference between sexes (*p ≤ 0.05 and ****p ≤ 0.0001). (B) Ultrasound imaging axial scans of the (i) right vagus nerve at rest and (ii) the final position of the neurodynamic test. The red arrow indicates the vagus nerve and the yellow arrow indicates the anterior tubercle of C6 in male or female participants (no differences between sexes were detected by USI, p = 0.54).
FIGURE 4
FIGURE 4
(A) Head orientation at the end of the neurodynamic test (R: head inclined on the right of the subject; L: head inclined on the left of the subject). (i) Inclination, (ii) rotation, and (iii) flexion/extension. The three dotted vertical lines in the graphs represent the three movements of the VN-NDT combined from the left to the right: upper cervical flexion, contralateral later flexion, and ipsilateral rotation, respectively. (B) ROC curves of symptoms related to vagal dysfunctions or autonomic peripheral neuropathies detected by the onset of tension (left) and pain (right) in the neck during the vagus nerve neurodynamic test. PHS, perceived health status; HR, heart rate.

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