The role of vagal neurocircuits in the regulation of nausea and vomiting

Abstract

Nausea and vomiting are among the most frequently occurring symptoms observed by clinicians. While advances have been made in understanding both the physiological as well as the neurophysiological pathways involved in nausea and vomiting, the final common pathway(s) for emesis have yet to be defined. Regardless of the difficulties in elucidating the precise neurocircuitry involved in nausea and vomiting, it has been accepted for over a century that the locus for these neurocircuits encompasses several structures within the medullary reticular formation of the hindbrain and that the role of vagal neurocircuits in particular are of critical importance. The afferent vagus nerve is responsible for relaying a vast amount of sensory information from thoracic and abdominal organs to the central nervous system. Neurons within the nucleus of the tractus solitarius not only receive these peripheral sensory inputs but have direct or indirect connections with several other hindbrain, midbrain and forebrain structures responsible for the co-ordination of the multiple organ systems. The efferent vagus nerve relays the integrated and co-ordinated output response to several peripheral organs responsible for emesis. The important role of both sensory and motor vagus nerves, and the available nature of peripheral vagal afferent and efferent nerve terminals, provides extensive and readily accessible targets for the development of drugs to combat nausea and vomiting.

Keywords: Brainstem; DVC; NTS; Vagus.

Fig. 1. Schematic diagram illustrating vagal neurocircuits involved in nausea and vomiting

While the exact neural pathways of the central pattern generator responsible for emesis are unknown, the NTS is the recipient of direct or indirect inputs from the abdominal and thoracic vagus, pharyngeal, glossopharyngeal and trigeminal nerves, the spinal tract, the area postrema, the hypothalamus, the cerebellum and vestibular/labyrinthine systems as well as the cerebral cortex and the critical role this nucleus plays in the integration, modulation and regulation of many autonomic reflexes involved in emesis cannot be overstated. Distinct neural outputs from the NTS co-ordinate several of the effector responses of emesis (swallowing, salivation, respiration, cardiovascular, gastrointestinal) in a precisely regulated temporal manner. For simplicity, not all neural pathways and regions are illustrated. AP, area postrema; NTS, nucleus tractus solitarius; Vestibular N., Vestibular Nucleus; Facial N., Facial Nucleus; DMV, dorsal motor nucleus of the vagus; N.Amb., Nucleus ambiguous; VRG, ventral respiratory group; Parabrachial N., Parabrachial nucleus.