Delineation of vagal emetic pathways: intragastric copper sulfate-induced emesis and viral tract tracing in musk shrews

Abstract

Signals from the vestibular system, area postrema, and forebrain elicit nausea and vomiting, but gastrointestinal (GI) vagal afferent input arguably plays the most prominent role in defense against food poisoning. It is difficult to determine the contribution of GI vagal afferent input on emesis because various agents (e.g., chemotherapy) often act on multiple sensory pathways. Intragastric copper sulfate (CuSO4) potentially provides a specific vagal emetic stimulus, but its actions are not well defined in musk shrews (Suncus murinus), a primary small animal model used to study emesis. The aims of the current study were 1) to investigate the effects of subdiaphragmatic vagotomy on CuSO4-induced emesis and 2) to conduct preliminary transneuronal tracing of the GI-brain pathways in musk shrews. Vagotomy failed to inhibit the number of emetic episodes produced by optimal emetic doses of CuSO4 (60 and 120 mg/kg ig), but the effects of lower doses were dependent on an intact vagus (20 and 40 mg/kg). Vagotomy also failed to affect emesis produced by motion (1 Hz, 10 min) or nicotine administration (5 mg/kg sc). Anterograde transport of the H129 strain of herpes simplex virus-1 from the ventral stomach wall identified the following brain regions as receiving inputs from vagal afferents: the nucleus of the solitary tract, area postrema, and lateral parabrachial nucleus. These data indicate that the contribution of vagal pathways to intragastric CuSO4-induced emesis is dose dependent in musk shrews. Furthermore, the current neural tracing data suggest brain stem anatomical circuits that are activated by GI signaling in the musk shrew.

Role of the abdominal vagus and hindbrain in inhalational anesthesia-induced vomiting

“…Similar to a prior study (Horn et al, 2014a), shrews received a sham-operation or abdominal vagotomy by random assignment (n = 11/group). Animals were anesthetized with isoflurane (2 to 3%) using an induction chamber followed by a nose cone during surgery.…”

“…Fluoro-Gold (Fluorochrome LLC, Denver, CO, USA), a retrograde neuronal tracer, was used to confirm the completeness of subdiaphragmatic vagotomy (Horn et al, 2014a; Powley et al, 1987). Animals were injected intraperitoneally with 0.2 ml of the tracer (1% solution in 0.15 NaCl).…”

“…The presence of Fluoro-Gold in the DMN was determined by fluorescent detection (Horn et al, 2014a). Images were collected using a Nikon epifluorescence microscope equipped with a wide-band UV filter and analyzed with ImageJ software (NIH; http://rsb.info.nih.gov/ij/) to assess the density of staining (gray level) in the left and right DMN relative to the adjacent NTS (higher ratio values, DMN/NTS, indicate more fluorescent staining in the DMN compared with the NTS).…”

Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea

“…The dorsal vagal complex (DVC), which is comprised of the nucleus tractus solitarius (NTS), the adjacent dorsal motor nucleus of the vagus, and area postrema, is often referred to as the chemoreceptor trigger zone in emesis literature [6]. DVC neural processing modulates descending vagal efferent communication to organs of the alimentary canal, thereby regulating gastric emptying and intestinal motility rates, as well as digestive enzymatic / hormonal secretions.…”

“…DVC neural processing modulates descending vagal efferent communication to organs of the alimentary canal, thereby regulating gastric emptying and intestinal motility rates, as well as digestive enzymatic / hormonal secretions. Fluctuations in these physiological processes are thought to contribute greatly to emesis and the feeling of nausea and other illness behaviors [6, 7]. However, in addition to processing aversive, stressful, and emetic stimuli [8, 9], the DVC is also critically involved in the normal regulation of energy balance [10].…”