Transdermal auricular vagus stimulation for the treatment of postural tachycardia syndrome

Abstract

Postural Tachycardia Syndrome (POTS) is a chronic disorder characterized by symptoms of orthostatic intolerance such as fatigue, lightheadedness, dizziness, palpitations, dyspnea, chest discomfort and remarkable tachycardia upon standing. Non-invasive transdermal vagal stimulators have been applied for the treatment of epilepsy, anxiety, depression, headache, and chronic pain syndromes. Anti-inflammatory and immunomodulating effects after transdermal vagal stimulation raised interest for applications in other diseases. Patients with sympathetic overactivity, reduced cardiac vagal drive and presence of systemic inflammation like POTS may benefit from tVNS. This article will address crucial methodological aspects of tVNS and provide preliminary results of its acute and chronic use in POTS, with regards to its potential effectiveness on autonomic symptoms reduction and heart rate modulation.

Keywords: Autonomic function; Postural tachycardia syndrome; Vagal stimulation.

Figure 1.

Simplified schematic of the innervation of the ear. The Cymba Concha and Concha Cavum are innervated by the Auricular Branch of the Vagus Nerve and therefore preferred anatomical regions for transdermal vagal stimulation (tVNS). The tragus and fossa triangularis have also been proposed as sites for tVNS.

Figure 2.

Transdermal stimulation of the auricular branch of the vagal nerve of the ear modulates vagal afferent inputs which activate regions of the brain such as the locus coeruleus, the thalamus, the prefrontal cortex, the postcentral gyrus, the posterior cingulate gyrus and the insula cortex. This can modulate perception and mood (1). Projection via nucleus tractus solitary (NTS) increases activity of neurons in the caudal ventrolateral medulla (CVLM), increases inhibition of sympathetic pacemaker neurons in the rostral ventrolateral medulla (RVLM), and increases vagal activity in the nucleus ambiguous (NA). Increased vagal activity and reduced sympathetic neural activity (SNA) to the sinus atrial node reduces heart rate (2). Vagal stimulation mobilizes the cholinergic anti-inflammatory pathway through sympathetic axons supplying the spleen. It increases norepinephrine (NE) release in the spleen. NE activates beta2 receptors expressed in splenic macrophages and attenuates cytokine production when signaling through nicotinic acetylcholine receptor 7 subunit (alpha7nAchR) is present (3). All these effects are beneficial for patients with postural tachycardia syndrome (POTS).

Figure 3.

Frequency response of high frequency component of heart rate variability (HF RRI) and R-R intervals (RRI) to randomized transdermal stimulation of the right auricular branch of Vagus nerve at subsensory levels in patients with POTS and low resting HF component. Values are expressed as mean±SD.

Figure 4.

Improvement of orthostatic intolerance (Tilt Time, left panel) and tendency of reduction of heart rate response (ΔHR) after transdermal stimulation of the right auricular branch of the vagus nerve at subsensory levels in patients with POTS and low resting HF component.

Fig. 5.

Dysautonomia symptoms and HR changes (Delta) after chronic tVNS. Individual values of COMPASS-31 domains and delta HR after 14-day tVNS are shown together with their mean ± SEM values. The reduction in dysautonomia symptom intensity is significant in Total Score and in Orthostatic Intolerance and Gastrointestinal symptom domains. The individual difference between supine and orthostatic heart rate was blunted, although not significantly, during POST evaluation. GI indicates gastrointestinal domain. OI, orthostatic intolerance. Delta HR, mean value of the individual differences between orthostatic and clinostatic heart rate. PRE, pre-treatment. POST, post-treatment. *P < 0.05 POST vs PRE; data are expressed as mean ± SEM.