Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol

Abstract

Stimulation of the vagus nerve, a parasympathetic nerve that controls the neuro-digestive, vascular, and immune systems, induces pain relief, particularly in clinical conditions such as headache and rheumatoid arthritis. Transmission through vagal afferents towards the nucleus of the solitary tract (NST), the central relay nucleus of the vagus nerve, has been proposed as the main physiological mechanism that reduces pain intensity after vagal stimulation. Chronic pain symptoms of fibromyalgia patients might benefit from stimulation of the vagus nerve via normalization of altered autonomic and immune systems causing their respective symptoms. However, multi-session non-invasive vagal stimulation effects on fibromyalgia have not been evaluated in randomized clinical trials. We propose a parallel group, sham-controlled, randomized study to modulate the sympathetic–vagal balance and pain intensity in fibromyalgia patients by application of non-invasive transcutaneous vagus nerve stimulation (tVNS) over the vagal auricular and cervical branches. We will recruit 136 fibromyalgia patients with chronic moderate to high pain intensity. The primary outcome measure will be pain intensity, and secondary measures will be fatigue, health-related quality of life, sleep disorders, and depression. Heart rate variability and pro-inflammatory cytokine levels will be obtained as secondary physiological measures. We hypothesize that multiple tVNS sessions (five per week, for 4 weeks) will reduce pain intensity and improve quality of life as a result of normalization of the vagal control of nociception and immune–autonomic functions. Since both vagal branches project to the NST, we do not predict significantly different results between the two stimulation protocols.

The effect of auricular vagus nerve stimulation on electroencephalography and electromyography measurements in healthy persons

“…Decreased alpha band power indicates dysfunction in the thalamocortical circuit, where inhibition of trivial information cannot be achieved ( Klimesch et al, 2007 ). Therefore, our results are consistent with studies supporting the idea that auricular VNS can be used as an alternative approach in the treatment of chronic pain for patients with FMS ( Martins et al, 2021 ; Molero- Chamizo et al, 2022 ).…”

Effect of transcutaneous auricular vagal nerve stimulation on the fatigue syndrome in patients with gastrointestinal cancers — FATIVA: a randomized, placebo-controlled pilot study protocol

“…Defining the control/sham group has been discussed in literature. While some suggest stimulation of entirely different body areas [ 57 ], others chose the earlobe, which is not innervated by the vagal nerve, for control stimulation [ 58 ]. However, stimulation of the earlobe or other parts of the ear might cause interfering muscle activation [ 59 , 60 ].…”

Non-Invasive Electric and Magnetic Brain Stimulation for the Treatment of Fibromyalgia

“…Invasive [ 81 ] and non-invasive [ 82 , 83 , 84 ] methods of vagal nerve stimulation have been shown to be effective in different neurological disorders. In this vein, non-invasive transcutaneous vagus nerve stimulation (tVNS) is a promising therapeutic approach because of its safety and efficacy profile [ 85 ]. Particularly, transcutaneous stimulation of the auricular and cervical branches of the vagal nerve induces modulatory effects on the activity of this nerve [ 86 , 87 ], with therapeutic impact in several pathologies [ 86 , 88 ].…”

“…Particularly, transcutaneous stimulation of the auricular and cervical branches of the vagal nerve induces modulatory effects on the activity of this nerve [ 86 , 87 ], with therapeutic impact in several pathologies [ 86 , 88 ]. Thus, the sympathetic and inflammatory dysregulation that appears to underlie fibromyalgia might be tackled non-invasively by tVNS [ 85 ], and some studies indeed suggest therapeutic effects of tVNS on pain and quality of life in patients with fibromyalgia [ 84 , 89 ].…”