The effects of non-invasive vagus nerve stimulation on immunological responses and patient reported outcome measures of fatigue in patients with chronic fatigue syndrome, fibromyalgia, and rheumatoid arthritis, by E Traianos, B Dibnah, D Lendrem, Y Clark, V Macrae, V Slater, K Wood, D Storey, B Simon, J Blake, J Tarn, WF Ng in Annals of the Rheumatic Diseases 2021;80:1057-1058
Research abstract:
Background:
Fatigue is reported as a common symptom among autoimmune and other chronic diseases such as fibromyalgia (FM), a long-term condition with uncertain pathophysiology. Previous studies from our group suggest that non-invasive vagus nerve stimulation (nVNS) may contribute to the improvement of patient reported outcome measures (PROMs) of fatigue in patients with primary Sjögren’s Syndrome.
Objectives:
This follow-up study uses the gammaCore device (electroCore) to assess the effect of nVNS on PROMs of fatigue and immune responses in chronic fatigue syndrome (CFS), FM and rheumatoid arthritis (RA).
Methods:
The study included thirteen CFS, fourteen FM and fifteen RA patients who used the gammaCore nVNS device twice daily over a 26-day period.
Pre- and post- nVNS bloods were drawn at baseline and final visits. Whole blood samples were stimulated with 2 ng/mL lipopolysaccharide (LPS) and the IL-6 and TNF-α cytokine concentrations were quantified at 24 hours. In addition, the epidermal growth factor (EGF), IFN-γ, IL-6, IP-10, MIP-1α, and TNF-α levels were measured in ‘pre-nVNS’ serum and flow cytometric profiles of whole blood immune cells were analysed.
The patient reported outcome measures (PROMs) recorded at each visit were the Visual Analogue Scale (VAS) (0-100 cm) of abnormal fatigue, Hospital Anxiety and Depression (HAD) Scale, Orthostatic Grading Scale, Epworth Sleepiness Scale (daytime sleepiness), and Profile of fatigue (PRO-F) for Physical and Mental fatigue. Paired t-tests were performed to assess for changes in PROMs, cytokine levels, and cell subset distribution and associations of cytokine response with PROMs were investigated by correlation analyses.
Results:
Eleven CFS, twelve FM and fourteen RA patients completed the study. There was a significant reduction in daytime sleepiness in CFS (p =0.0321) and FM (p =0.0294) patients between the final and baseline visits and a significant reduction in HAD depression (p =0.0413) in FM (Fig.1). Improvement in VAS for abnormal fatigue, HAD-Anxiety, HAD-Depression, PRO-F Physical and Mental fatigue was observed in all three groups over the study period with a reduction in VAS fatigue in 64% of CFS, 67% of FM and 62% of RA patients.
There were no significant changes in the immune cell subsets or in cytokine response. Finally, higher baseline pre-nVNS supernatant IL-6 levels were predictive of an improvement in VAS fatigue (p =0.0006), Daytime Sleepiness (p =0.0466) and PRO-F Physical fatigue (p =0.0196) in RA, while higher baseline TNF-α levels were predictive of an improvement in VAS fatigue (p =0.0003), Daytime Sleepiness (p =0.0380), Orthostatic (p =0.0281) and PRO-F Physical fatigue (p =0.0007) in FM.
Conclusion:
Our findings suggest that nVNS may contribute to the improvement of PROMs of fatigue in CFS, FM and RA. NVNS led to significant reductions in daytime sleepiness in CFS and FM, and depression in FM. Further studies and a larger sample size are needed to investigate the potential effects of nVNS on diseases characterised by persistent fatigue.
