ABSTRACT
COVID-19 presented a renewed awareness of the importance of smell, including the striking impact of smell loss on daily functioning, as well as the lack of available evidencebased interventions to improve smell. While medical and surgical treatments exist for inflammatory-related smell loss, interventions to treat loss due to other etiologies are limited. Given the role of the intranasal trigeminal system in smell function, we conducted a proof-of-concept study to determine the effects of electrical stimulation of the trigeminal nerve (TNS) on sensitivity to phenyl ethyl alcohol (PEA) and guaiacol (GUA), 2 odorants with low and high trigeminal properties, respectively. TNS is an emerging form of “bottom-up” brain stimulation in which low-level electrical current is delivered to superficial trigeminal nerve branches innervating the face and forehead. Twenty healthy adults (8M/12F, 27±8.1 years old) were recruited from MUSC and the surrounding community to participate in this double-blind, placebo-controlled, pilot. PEA and GUA thresholds were determined at baseline, immediately postintervention, and again 30-min post-intervention. In a randomized cross-over design, participants received active and sham TNS on separate visits. Results indicated a significant stimulation x odor x time interaction (F[2,76]=3.56, p=.024, η 2=.093). Detection of GUA, but not PEA, was significantly enhanced by active, but not sham, TNS (16% and 9% increase from baseline at the 1st and 2nd follow-up time points respectively). TNS is safe, noninvasive, inexpensive, and easy to administer, rendering it highly scalable. Future study should determine the full effects and durability of TNS on smell function across different stimulation parameters, odorants, and patient populations.