Fig. 2.

A summary of the main pathways implicated in induction of nausea and vomiting and the neurotransmitters/signalling molecules (see Stern et al., 2011; Sanger and Andrews, 2018; Zhong et al., 2021 for details and references). The main inputs (vestibular system, area postrema [AP] and abdominal vagal afferents) inducing nausea and vomiting converge on the nucleus tractus solitarius (NTS). The AP is outside the blood brain barrier and can be activated by a range of circulating substance. For example: Growth Differentiation Factor 15 (GDF15) from liver, macrophages (M), kidney (K) and placenta; Prostaglandin E₂ (PGE₂) and Interleukin-2 (IL-2) from inflamed/damaged tissue; Glucagon –like peptide-1 (GLP-1) and cholecystokinin (CCK) from Enteroendocrine Cells (EEC). Substances released from the EEC cells, particularly 5-hydroxytryptmaine (5-HT) and substance P (SP) can also act locally to activate the vagal afferents which can also be sensitised by inflammatory mediators. Red boxes indicate key receptors implicated in emesis in the vestibular system, dorsal vagal complex (NTS ​+ ​AP) and abdominal vagal afferent activation. Cartoon from Sanger and Andrews (2018). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)