title: Role of the abdominal vagus and hindbrain in inhalational anesthesia-induced vomiting.
abstract: The incidence of postoperative nausea and vomiting (PONV) can be as high as 80% in patients with risk factors (e.g., females, history of motion sickness). PONV delays postoperative recovery and costs several hundred million dollars annually. Cell-based assays show that halogenated ethers (e.g., isoflurane) activate 5-HT3receptors, which are found on gastrointestinal vagal afferents and in the hindbrain - key pathways for producing nausea and vomiting. This project evaluated the role of the vagus and activation of the hindbrain in isoflurane-induced emesis in musk shrews, a small animal model with a vomiting reflex, which is lacking in rats and mice. Sham-operated and abdominal vagotomized shrews were exposed to 1 to 3% isoflurane to determine effects on emesis; vagotomy was confirmed by lack of vagal transport of the neuronal tracer Fluoro-Gold. In an additional study, shrews were exposed to isoflurane and hindbrain c-Fos was measured at 90min after exposure using immunohistochemistry. There were no statistically significant effects of vagotomy on isoflurane-induced emesis compared to sham-operated controls. Isoflurane exposure produced a significant increase in c-Fos-positive cells in the nucleus of the solitary tract and vestibular nuclei but not in the area postrema or dorsal motor nucleus. These results indicate that the abdominal vagus plays no role in isoflurane-induced emesis and suggest that isoflurane activates emesis by action on the hindbrain, as shown by c-Fos labeling. Ultimately, knowledge of the mechanisms of inhalational anesthesia-induced PONV could lead to more targeted therapies to control PONV.
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Ragini G
authors.initials: RG
authors.lastname: Gupta
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Schafer
authors.affiliation: AgroSup, Dijon, France.
authors.forename: Yolande
authors.initials: Y
authors.lastname: Ramaroson
authors.affiliation: Biobehavioral Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Sciullo
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Biobehavioral Oncology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA; Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, United States. Electronic address: chorn@pitt.edu.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Horn
mesh_terms: D000769:Anesthesia, Inhalation / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004639:Emetics / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007530:Isoflurane / Q000009:adverse effects / Q000494:pharmacology; D023421:Models, Animal; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D012249:Rhombencephalon / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D012788:Shrews; D013266:Stilbamidines; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D014839:Vomiting / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018685:Anesthetics, Inhalation; D004639:Emetics; D016760:Proto-Oncogene Proteins c-fos; D013266:Stilbamidines; D007530:Isoflurane
keywords: Anesthesiology; Isoflurane; NTS; Perioperative care; Post-anesthesia care unit; Post-operative nausea and vomiting