Vagus Nerve Stimulation May Improve Fatigue Symptoms in Sjogren Syndrome

Noninvasive vagus nerve stimulation significantly reduced fatigue in patients with primary Sjogren syndrome.

Noninvasive stimulation of the vagus nerve (nVNS) was associated with an improvement in fatigue symptoms among patients with Sjogren syndrome, according to study findings published in Neuromodualtion.

Primary Sjogren syndrome (PSS), a chronic autoimmune disease, is associated with poor quality of life (QoL) and a key independent predictor for poor health-related QoL is fatigue. Previous research has found evidence that nVNS stimulation improved symptoms of fatigue.

To further investigate the relationship between nVNS and fatigue in PSS, researchers from Newcastle University in the United Kingdom recruited patients with PSS (N=40). Participants were randomized to receive active or sham nVNS. On days 1, 2, or 3, and 56, participants were evaluated for patient-reported outcome measures (PROMs), immune response, electroencephalography (EEG), muscle bioenergetics, and heart rate variability.

At the second visit, participants practiced and first used their assigned active or sham stimulation device. The gammaCore nVNS devices delivered five 5000 Hz pulses at a rate of 25 Hz for up to 120 seconds in an approximately sine wave. The sham device looked identical to the active device and delivered a similar buzzing sensation to the skin without stimulating the vagus nerve.

Directly after device use, fatigue levels correlate with measures of alpha reactivity, suggesting modulation of cholinergic system integrity as a mechanism of action for nVNS.

Compared with baseline, the active stimulation was associated with significantly greater improvement to Profile of Fatigue (PRO-F)-Physical (P =.02), PRO-F-Mental (P =.02), and visual analogue scale (VAS) fatigue (P =.04) scores relative to the sham stimulation. No other significant changes in PROM scores were observed.

At neurocognitive testing, the active stimulation was associated with greater backwards digit span improvements (P =.03) and tended to improve total digit span (P =.06) compared with control individuals.

The active nVNS stimulation correlated with a median decrease in interleukin (IL)-6 of 168 pg/mL compared with a median increase of 452 pg/mL among control individuals (P =.02).

At EEG, a significant negative correlation was observed between fatigue VAS scores and alpha reactivity in the frontal (r, -0.91; P <.01), central (r, -0.79; P =.02), and posterior cortical (r, -0.71; P =.05) regions among participants who received active vagus stimulation.

During the experiment, no significant effects on muscle bioenergetics or heart rate variability were observed.

The major limitation of this study was that not all participants completed the study.

These data indicated that nVNS improved fatigue among patients with PSS. It still remains unclear what is the specific mechanism of this association. “Directly after device use, fatigue levels correlate with measures of alpha reactivity, suggesting modulation of cholinergic system integrity as a mechanism of action for nVNS,” the researchers stated.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Tarn J, Evans E, Traianos E, et al. The effects of noninvasive vagus nerve stimulation on fatigue in participants with primary Sjögren’s syndrome. Neuromodulation. Published online October 26, 2022. doi:10.1016/j.neurom.2022.08.461