title: Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex.
abstract: The beneficial effects of trigeminal nerve stimulation (TNS) on several neurological disorders are increasingly acknowledged. Hypothesized mechanisms include the modulation of excitability in networks involved by the disease, and its main site of action has been recently reported at brain stem level. Aim of this work was to test whether acute TNS modulates brain stem plasticity using the blink reflex (BR) as a model. The BR was recorded from 20 healthy volunteers before and after 20 min of cyclic transcutaneous TNS delivered bilaterally to the infraorbital nerve. Eleven subjects underwent sham-TNS administration and were compared to the real-TNS group. In 12 subjects, effects of unilateral TNS were tested. The areas of the R1 and R2 components of the BR were recorded before and after 0 (T0), 15 (T15), 30 (T30), and 45 (T45) min from TNS. In three subjects, T60 and T90 time points were also evaluated. Ipsi- and contralateral R2 areas were significantly suppressed after bilateral real-TNS at T15 (p = 0.013), T30 (p = 0.002), and T45 (p = 0.001), while R1 response appeared unaffected. The TNS-induced inhibitory effect on R2 responses lasted up to 60 min. Real- and sham-TNS protocols produced significantly different effects (p = 0.005), with sham-TNS being ineffective at any time point tested. Bilateral TNS was more effective (p = 0.009) than unilateral TNS. Acute TNS induced a bilateral long-lasting inhibition of the R2 component of the BR, which resembles a long-term depression-like effect, providing evidence of brain stem plasticity produced by transcutaneous TNS. These findings add new insight into mechanisms of TNS neuromodulation and into physiopathology of those neurological disorders where clinical benefits of TNS are recognized.
authors.affiliation: Neurological Clinic, Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 10, 07100, Sassari, Italy. gpilurzi@uniss.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Pilurzi
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100, Sassari, Italy. bmercante@uniss.it.
authors.forename: Beniamina
authors.initials: B
authors.lastname: Mercante
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100, Sassari, Italy. fratempo@hotmail.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ginatempo
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria Monserrato, 09042, Monserrato, Italy. follesa@unica.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Follesa
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100, Sassari, Italy. tolue@uniss.it.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Tolu
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/b, 07100, Sassari, Italy. deriuf@uniss.it.
authors.forename: Franca
authors.initials: F
authors.lastname: Deriu
mesh_terms: D000328:Adult; D001767:Blinking / Q000502:physiology*; D004576:Electromyography / Q000379:methods; D005260:Female; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D014276:Trigeminal Nerve / Q000502:physiology*; D055815:Young Adult
keywords: Blink reflex; Brain stem plasticity; Cranial nerve stimulation; Long-term depression; Neuromodulation; Trigeminal nerve stimulation