Research on nausea and vomiting has relied on using animal models to mimic the anatomy and neuropharmacologic features of the human body. The physiologic mechanism of nausea is a complex process that has yet to be fully elucidated. There are four general pathways that are activated by specific triggers in the human body that go on to create the sensation of nausea and vomiting. * Central nervous system (CNS): Stimuli can affect areas of the CNS including the cerebral cortex and the limbic system. These areas are activated by elevated intracranial pressure, irritation of the meninges (i.e. blood or infection), and extreme emotional triggers such as anxiety. The supratentorial region is also responsible for the sensation of nausea. * Chemoreceptor trigger zone (CTZ): The CTZ is located in the area postrema in the floor of the fourth ventricle within the brain. This area is outside the blood brain barrier, and is therefore readily exposed to substances circulating through the blood and cerebral spinal fluid. Common triggers of the CTZ include metabolic abnormalities, toxins, and medications. Activation of the CTZ is mediated by dopamine (D2) receptors, serotonin (5HT3) receptors, and neurokinin receptors (NK1). * Vestibular system: This system is activated by disturbances to the vestibular apparatus in the inner ear. These include movements that cause motion sickness and dizziness. This pathway is triggered via histamine (H1) receptors and acetylcholine (ACh) receptors. * Peripheral Pathways: These pathways are triggered via chemoreceptors and mechanoreceptors in the gastrointestinal tract, as well as other organs such as the heart and kidneys. Common activators of these pathways include toxins present in the gastrointestinal lumen and distension of the gastrointestinal lumen from blockage or dysmotility of the bowels. Signals from these pathways travel via multiple neural tracts including the vagus, glossopharyngeal, splanchnic, and sympathetic nerves. Signals from any of these pathways then travel to the brainstem, activating several structures including the nucleus of the solitary tract, the dorsal motor nucleus of the vagus, and central pattern generator. These structures go on to signal various downstream effects of nausea and vomiting. The body's motor muscle responses involve halting the muscles of the gastrointestinal tract, and in fact causing reversed propulsion of gastric contents towards the mouth while increasing abdominal muscle contraction. Autonomic effects involve increased salivation and the sensation of feeling faint that often occurs with nausea and vomiting. Pre-nausea pathophysiology It has been described that alterations in heart rate can occur as well as the release of vasopressin from the posterior pituitary.
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