Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

Abstract

Nausea and vomiting are amongst the most common symptoms encountered in medicine as either symptoms of diseases or side effects of treatments. In a more biological setting they are also important components of an organism's defences against ingested toxins. Identification of treatments for nausea and vomiting and reduction of emetic liability of new therapies has largely relied on the use of animal models, and although such models have proven invaluable in identification of the anti-emetic effects of both 5-hydroxytryptamine3 and neurokinin1 receptor antagonists selection of appropriate models is still a matter of debate. The present paper focuses on a number of controversial issues and gaps in our knowledge in the study of the physiology of nausea and vomiting including: The choice of species for the study of emesis and the underlying behavioural (e.g. neophobia), anatomical (e.g. elongated, narrow abdominal oesophagus with reduced ability to shorten) and physiological (e.g. brainstem circuitry) mechanisms that explain the lack of a vomiting reflex in certain species (e.g. rats); The choice of response to measure (emesis[retching and vomiting], conditioned flavour avoidance or aversion, ingestion of clay [pica], plasma hormone levels[e.g. vasopressin], gastric dysrhythmias) and the relationship of these responses to those observed in humans and especially to the sensation of nausea; The stimulus coding of nausea and emesis by abdominal visceral afferents and especially the vagus-how do the afferents encode information for normal postprandial sensations, nausea and finally vomiting?; Understanding the central processing of signals for nausea and vomiting is particularly problematic in the light of observations that vomiting is more readily amenable to pharmacological treatment than is nausea, despite the assumption that nausea represents "low" intensity activation of pathways that can evoke vomiting when stimulated more intensely.

Extrinsic primary afferent signalling in the gut

“…At least some of this contribution is mediated by mucosal afferents that are sensitive to 5-hydroxytryptamine, released by a variety of toxins from enterochromaffin cells. 152,153 These same afferents might also be sensitive to nutrients, 154 including simple carbohydrates.…”

Food preferences and aversions in human health and nutrition: how can pigs help the biomedical research?

“…As a result, the ferret has been used as an alternative model to rodents for chemotherapy-induced emesis (Andrews and Horn, 2006). Those pharmacological studies enabled the identification of efficient antiemetic agents such as serotonin type 3 receptor antagonists (anti-5HT3) or neurokinin type 1 receptor antagonists (anti-NK1) that are frequently used during chemotherapy treatments to inhibit nausea and vomiting in cancer patients (Durand et al, 2009).…”

Why is the neurobiology of nausea and vomiting so important?

“…Furthermore, the neural pathways mediating CFA are inherently difficult to assess because of the long delay between input and response and the complexity of a system that also depends on learning and memory. Even though rodents lack a vomiting response they display pica when injected with toxins or subjected to strong motion, and pica can be inhibited by anti-emetic drugs (review, Andrews & Horn, 2006). Research suggests a relationship between pica, CFA, and emesis but the neurobiological substrates remain to be determined (Smith, Friedman, & Andrews, 2001;Rabin & Hunt, 1992).…”

“…Emesis, along with diarrhea, helps rid the gastrointestinal tract of dangerous ingested toxins. The vomiting response is present in many species, appearing in most vertebrates (including representative members of fish, amphibia, reptiles, birds, and mammals, see Andrews, Axelsson, Franklin, & Holmgren, 2000;Andrews & Horn, 2006;Borison, Borison, & McCarthy, 1981) and at least one invertebrate, the gastropod pleurobanchaea (McClellan, 1983). However, the broad assessment of the emetic response across species is hampered by the problem of distinguishing emesis from processes of regurgitation and rumination; emesis is functionally different and likely represents a more forceful ejection of gastric contents.…”

“…It is worth noting however that only a few strains of these species have been tested for emesis, using a limited set of stimuli, and it is unknown whether all members of these species lack the response. The possibility exists that rodents possess a degenerate "emetic" response rather than an absent one (Andrews & Horn, 2006). There is an isolated report of "retching" in mice (Furukawa & Yamada, 1980) and rats have a gag reflex, which has similar features to a single retch, triggered by mechanical stimulation of the pharynx (Andrew, 1956).…”