Electrical Stimulation of the Infraorbital Nerve Induces Diving Reflex in a Dose-Controlled Manner

The "diving reflex" (DR) is a very powerful autonomic reflex that facilitates survival in hypoxic/anoxic conditions and could trigger multifaceted physiologic effects for the treatment of various diseases by modulating the cardiovascular, respiratory, and nervous systems. The DR can be induced by cold water or noxious gases applied to the anterior nasal mucosa and paranasal regions, which can stimulate trigeminal thermo- or chemo-receptors to send afferent signals to medullary nuclei which mediate the sympathetic and parasympathetic nervous systems. Although promising, these approaches have yet to be adopted in routine clinical practice due to the inability to precisely control exposure-response relationships, lack of reproducibility, and difficulty implementing in a clinical setting. In this study, we present the ability of electrical Trigeminal (Infraorbital) Nerve Stimulation (eTINS) to induce the DR in a dose-controllable manner. We found that eTINS not only triggered specific physiological changes compatible with the pattern of "classic" DR observed in animals/humans, but also controlled the induced-DR at varying levels. This study demonstrates, for the first time, that the intensity of the DR is controllable by dose and opens possibility to investigate its protective mechanism against various pathologies in well-controlled research settings.