nVNS sham significantly affects the trigeminal-autonomic reflex: A randomized controlled study.

Area of Science:

• Neuroscience
• Physiology

Background:

• Clinical trials of noninvasive vagal nerve stimulation (nVNS) have reported significant placebo effects.
• The underlying mechanisms for these placebo effects, particularly the role of sham devices, require further investigation.

Purpose of the Study:

• To investigate whether sham devices used in noninvasive vagal nerve stimulation (nVNS) trials actively modulate the trigeminal-autonomic reflex.
• To determine if observed placebo effects in nVNS trials can be attributed to sham device stimulation.

Main Methods:

• A randomized, controlled, single-blind, within-participant study involving 28 healthy individuals.
• Four conditions were tested: no stimulation, active nVNS, sham stimulation of the posterior neck (sham I), and sham nVNS (sham II).
• Parasympathetic output was measured via lacrimation induced by kinetic oscillation stimulation (KOS) and quantified using the Schirmer II test.

Main Results:

• Noninvasive vagal nerve stimulation (nVNS) significantly reduced KOS-induced lacrimation compared to no stimulation and sham I.
• Sham nVNS (sham II) also significantly reduced lacrimation, with no significant difference observed between active nVNS and sham II.
• Both active nVNS and sham devices demonstrated modulation of the trigeminal-autonomic reflex.

Conclusions:

• The findings suggest that both active noninvasive vagal nerve stimulation (nVNS) and sham devices can modulate the trigeminal-autonomic reflex.
• This modulation by sham devices may account for the substantial placebo effects observed in previous nVNS clinical trials.
• Stimulation of the posterior neck is proposed as a potentially effective sham condition for future nVNS research.