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

Zhong, Weixia; Shahbaz, Omar; Teskey, Garrett; Beever, Abrianna; Kachour, Nala; Venketaraman, Vishwanath; Darmani, Nissar A.

doi:10.3390/ijms22115797

Cited by 117 publications

(95 citation statements)

References 299 publications

(470 reference statements)

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“…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.…”

Section: Interesting Brain Areasmentioning

confidence: 99%

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

2022

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Cybersickness still poses a significant challenge to the widespread usage of virtual reality, leading to different levels of discomfort and potentially breaking the immersive experience. Researchers have attempted to discover the possible fundamental causes of cybersickness for years. Despite the longstanding interest in the research field, inconsistent results have been drawn on the contributing factors and solutions to combating cybersickness. Moreover, little attention has been paid to individual susceptibility. A consolidated explanation remains under development, requiring more empirical studies with robust and reproducible methodologies. This review presents an integrated survey connecting the findings from previous review papers and the state of the art involving empirical studies and participants. A literature review is then presented, focusing on the practical studies of different contributing factors, the pros and cons of measurements, profiles of cybersickness, and solutions to reduce this phenomenon. Our findings suggest a lack of considerations regarding user susceptibility and gender balance in between groups studies. In addition, incongruities among empirical findings raised concerns. We conclude by suggesting points of insights for future empirical investigations.

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Section: Interesting Brain Areasmentioning

confidence: 99%

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

2022

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“…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 ].…”

Section: Current Clinically Used 5-ht 3 Receptor-based Therapiesmentioning

confidence: 99%

“…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 ].…”

Section: Current Clinically Used 5-ht 3 Receptor-based Therapiesmentioning

confidence: 99%

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

Irving

Turek

Kettle

et al. 2021

IJMS

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5-hydroxytryptamine type 3 (5-HT3) receptors are ligand gated ion channels, which clearly distinguish their mode of action from the other G-protein coupled 5-HT or serotonin receptors. 5-HT3 receptors are well established targets for emesis and gastrointestinal mobility and are used as adjunct targets in treating schizophrenia. However, the distribution of these receptors is wider than the nervous system and there is potential that these additional sites can be targeted to modulate inflammatory and/or metabolic conditions. Recent progress in structural biology and pharmacology of 5-HT3 receptors have provided profound insights into mechanisms of their action. These advances, combined with insights into clinical relevance of mutations in genes encoding 5-HT3 subunits and increasing understanding of their implications in patient’s predisposition to diseases and response to the treatment, open new avenues for personalized precision medicine. In this review, we recap on the current status of 5-HT3 receptor-based therapies using a biochemical and physiological perspective. We assess the potential for targeting 5-HT3 receptors in conditions involving metabolic or inflammatory disorders based on recent findings, underscoring the challenges and limitations of this approach.

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Sun

2021

IJERPH

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Motion sickness is a common central nervous system response, the primary sign of which is vomiting. Its susceptibility varies between individuals. To find predictive factors, we investigated the association of ADRA2A rs1800544 and HTR3B rs3758987 with motion sickness susceptibility and examined their mRNA changes during actual voyages. A total of 315 healthy college students were enrolled for SNP genotyping by the PCR-RFLP method. Blood samples were collected from another 42 subjects during two separate voyages to detect their mRNA expression changes at three time points. The frequency of the rs1800544 GG genotype in the susceptibility group was significantly higher (52.26%), and allele G increased the risk of motion sickness (OR = 1.585, 95% CI = 1.136–2.208). In the logistic regression model, the rs3758987 CC+TC genotype and rs1800544 GG genotype increased the risk of motion sickness-induced vomiting (OR = 2.105, 95% CI = 1.112–3.984; OR = 1.992, 95% CI = 1.114–3.571). The ADRA2A mRNA baseline was lower in the GG carriers and the HTR3B mRNA baseline was lower in the TC/CC carriers before sailing, then increased significantly within 24 h and then decreased after a long-term voyage. People carrying the rs1800544 GG genotype seem more susceptible to motion sickness. In combination with the incidence of vomiting during the actual-voyage experiments, our results indicate the involvement of rs1800544 and rs3758987 in motion sickness-induced vomiting.

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

Cited by 117 publications

References 299 publications

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

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

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

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

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