Measuring the nausea-to-emesis continuum in non-human animals: refocusing on gastrointestinal vagal signaling

Abstract

Nausea and vomiting are ubiquitous as drug side effects and symptoms of disease; however, the systems that determine these responses are arguably designed for protection against food poisoning occurring at the level of the gastrointestinal (GI) tract. This basic biological pathway using GI vagal afferent communication to the brain is not well understood. Part of this lack of insight appears to be related to current experimental approaches, such as the use of experimental drugs, including systemic chemotherapy and brain penetrant agents, which activate parts of the nausea and vomiting system in potentially unnatural ways. Directly related to this issue is our ability to understand the link between nausea and vomiting, which are sometimes argued to be completely separate processes, with nausea as an unmeasurable response in animal models. An argument is made that nausea and emesis are the efferent limbs of a unified sensory input from the GI tract that is likely to be impossible to understand without more specific animal electrophysiological experimentation of vagal afferent signaling. The current paper provides a review on the use of animal models and approaches to define the biological systems for nausea and emesis and presents a potentially testable theory on how these systems work in combination.

Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron

“…Emetogenic stimuli also induce gastric dysmotility. This has been used as an indirect marker of nausea in rodents but occurs likewise in non‐rodent species . Similar to previous reports, our study demonstrated that cisplatin at 6 mg kg −1 reduced gastric emptying and produced gastric distension, mainly due to the distension of the forestomach.…”

“…This has been used as an indirect marker of nausea in rodents 20,21,43 but occurs likewise in non-rodent species. 44,45 Similar to previous reports, 15,20,21,46 our study demonstrated that cisplatin at 6 mg kg −1 reduced gastric emptying and produced gastric distension, mainly due to the distension of the forestomach. Gastric dysmotility associated with this high dose of cisplatin was observed as soon as 20 minutes after administration 21 and lasted for at least 3 days.…”

Nausea as a sentinel symptom for cytotoxic chemotherapy effects on the gut-brain axis among women receiving treatment for recurrent ovarian cancer: an exploratory analysis

“…In what are now largely separate silos of research, the importance of vagal function has been implicated in studies of: microbiome influences on symptom experience [44]; appetite [45]; nausea and vomiting [46]; fatigue [47]; drowsiness and sleep problems [48]; and peripheral pain sensation [49]. It is also important to note that nausea does not require a precipitating impact on the gut; nausea can be provoked by effects in the central nervous system components of the gut-brain axis.…”

What is nausea? A historical analysis of changing views

“…However, individuals often experience nausea without vomiting (Horn, 2014; Lackner, 2014). Moreover, individuals describe nausea in various ways (Graybiel et al, 1968; Muth et al, 1996), in accordance with the wide range of perceptions that can occur prior to vomiting.…”