Abstract
BackgroundA growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. Frequency is one of the key stimulation parameters. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine.MethodsTwenty-four episodic migraineurs without aura (21 females) were recruited for the single-blind, crossover, functional magnetic resonance imaging (fMRI) study. Each participant attended two separate fMRI scan sessions, one for 1 Hz and another for 20 Hz taVNS, in a random order. Seed-based functional connectivity analysis was applied using the ventrolateral periaqueductal gray (PAG) as the region of interest.ResultsCompared with the pre-taVNS resting state, continuous 1 Hz taVNS (during) produced a significant increase in functional connectivity between the PAG and the bilateral middle cingulate cortex (MCC), right precuneus, left middle frontal gyrus (MFG), and left cuneus. Compared with 20 Hz taVNS, 1 Hz taVNS produced greater PAG connectivity increases with the MCC, right precuneus/posterior cingulate cortex, left insula, and anterior cingulate cortex (ACC). A significant negative correlation was observed between the number of migraine attacks in the previous 4 weeks and the PAG-MCC functional connectivity in the pre-taVNS resting-state before 1 Hz taVNS.ConclusionsOur findings suggest that taVNS with different frequencies may produce different modulation effects on the descending pain modulation system, demonstrating the important role of stimulation frequency in taVNS treatment.
Highlights
A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation may relieve symptoms of migraineurs
In an earlier study [35], we investigated the resting state functional connectivity of the periaqueductal grey (PAG), a key region in the descending pain modulation system (DPMS) in healthy subjects and found significant rsFC between the periaqueductal gray (PAG) and central regions of the DPMS, such as the anterior cingulate cortex (ACC), rostroventral medulla (RVM) and anterior insula, demonstrating the feasibility of using functional connectivity methods to non-invasively investigate the DPMS in humans
VlPAG‐based functional connectivity analysis results Compared with pre-transcutaneous auricular vagus nerve stimulation (taVNS) resting state, 1 Hz continuous taVNS produced significant functional connectivity increases between the ventrolateral periaqueductal gray (vlPAG) and the bilateral middle cingulate cortex (MCC), the right precuneus, the left middle frontal gyrus (MFG), and the left cuneus (Table 2, Fig. 2A)
Summary
A growing body of evidence suggests that transcutaneous auricular vagus nerve stimulation (taVNS) may relieve symptoms of migraineurs. The aim of this study is to investigate the modulation effect of taVNS frequency on the descending pain modulation system (DPMS) in patients with migraine. Direct stimulation of the nerve fibers on the ear may produce an effect similar to classic vagus nerve stimulation. This plausibility has led to the development of transcutaneous auricular vagus nerve stimulation (taVNS), a noninvasive, low-cost, and implementable alternative to classic vagus nerve stimulation [12,13,14,15]. A growing body of evidence suggests that taVNS can induce antinociception, which may affect peripheral and central nociception, inflammatory responses, autonomic activity, and pain-related behavior [1, 16,17,18]
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