Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems

Abstract

Nausea and vomiting are common gastrointestinal complaints that can be triggered by diverse emetic stimuli through central and/or peripheral nervous systems. Both nausea and vomiting are considered as defense mechanisms when threatening toxins/drugs/bacteria/viruses/fungi enter the body either via the enteral (e.g., the gastrointestinal tract) or parenteral routes, including the blood, skin, and respiratory systems. While vomiting is the act of forceful removal of gastrointestinal contents, nausea is believed to be a subjective sensation that is more difficult to study in nonhuman species. In this review, the authors discuss the anatomical structures, neurotransmitters/mediators, and corresponding receptors, as well as intracellular emetic signaling pathways involved in the processes of nausea and vomiting in diverse animal models as well as humans. While blockade of emetic receptors in the prevention of vomiting is fairly well understood, the potential of new classes of antiemetics altering postreceptor signal transduction mechanisms is currently evolving, which is also reviewed. Finally, future directions within the field will be discussed in terms of important questions that remain to be resolved and advances in technology that may help provide potential answers.

A review of cybersickness in head-mounted displays: raising attention to individual susceptibility

“…It is now understood that gut-brain axis plays an important role in gastrointestinal regulation such as the Fig. 2 Total number of papers identified by database and numbers of papers shortlisted as relevant for review initiation and maintenance of nausea and vomiting (Zhong et al 2021). Since high sensitive individuals tend to have nausea or vertigo sensations when cybersick, studying the gut-brain interaction may be the key to unfold the mystery of individual susceptibility.…”

Tapping into 5-HT3 Receptors to Modify Metabolic and Immune Responses

“…The evolutionary development of this 5-HT 3 receptor antagonist class has generated many structural analogs designed to improve selectivity, reduce side effects, and improve ligand pharmacodynamics for delayed emesis compared to acute emesis, bringing additional ‘setron’ ligands, such as granisetron, ramosetron, dolasetron, tropisetron, and the second-generation ligand, palonosetron. These advances have been thoroughly reviewed [ 8 , 19 , 21 , 22 , 151 , 217 , 218 , 219 ]. This drug class possesses excellent antiemetic treatment and prophylaxis effects due to their ability to inhibit serotonin activity on both the central nervous system in the chemoreceptor trigger zone and peripherally on gastrointestinal vagal nerve terminals [ 22 , 30 , 217 , 218 , 220 ].…”

“…These advances have been thoroughly reviewed [ 8 , 19 , 21 , 22 , 151 , 217 , 218 , 219 ]. This drug class possesses excellent antiemetic treatment and prophylaxis effects due to their ability to inhibit serotonin activity on both the central nervous system in the chemoreceptor trigger zone and peripherally on gastrointestinal vagal nerve terminals [ 22 , 30 , 217 , 218 , 220 ]. Over time, their clinical usage has expanded beyond chemotherapy induced emesis to nausea and vomiting provoked by radiation therapy and post-operative procedures in adult and pediatric patients [ 30 , 116 , 136 , 217 ] and also pregnancy induced emesis [ 217 ].…”

The Predictive Role of ADRA2A rs1800544 and HTR3B rs3758987 Polymorphisms in Motion Sickness Susceptibility

“…Vomiting is the typical symptom of MS [ 26 ]. Generally, stimulus signals are transmitted from the intestines to the brain through nerves, activating the vomiting center and causing the individual to vomit [ 27 , 28 ]. The enteric nervous system (ENS) is now considered a third component of the autonomic nervous system.…”

“…The 5-hydroxytryptamine type 3B receptor (HTR3B) plays an important role in this progress [ 30 ]. The 5-HT3 receptor mediates vomiting, which occurs via the activation of Ca2+/CaMKII-dependent ERK1/2 signaling [ 27 ]. Genetic polymorphisms of the HTR3B may affect the expression or function of the HTR3 complex, and the signaling of serotonin.…”