Transcutaneous trigeminal nerve stimulation induces a long-term depression-like plasticity of the human blink reflex.

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.