Pathophysiology of Vomiting

The vomiting center, also called the emetic center, is located in the medulla of the brainstem and coordinates the act of vomiting. This area is rich in muscarinic M1, histamine H1, neurokinin 1 (NK1), and serotonin 5-HT3 receptors. It integrates signals from multiple sources including the chemoreceptor trigger zone, solitary tract nucleus, vestibular apparatus, cerebral cortex, and gastrointestinal afferent nerves to initiate the vomiting reflex.

The chemoreceptor trigger zone (CTZ) is located outside the blood-brain barrier and detects stimuli in the blood and cerebrospinal fluid. Rich in dopamine and opioid receptors, the CTZ identifies cytotoxic drugs, opioids, and other harmful substances. Upon detection, it signals the vomiting center to initiate the vomiting reflex, making it a primary site of action for many antiemetic drugs.

Vagal and spinal afferent nerves in the gastrointestinal tract contain serotonin receptors. When the GI mucosa detects pathogens or toxins, it releases serotonin, activating these afferent nerves. The signals transmit through the chemoreceptor trigger zone or solitary tract nucleus to the vomiting center, contributing to chemotherapy-induced nausea and vomiting and other GI-related emesis.

The inner ear's vestibular apparatus sends signals to the chemoreceptor trigger zone via cranial nerve VIII, causing motion sickness. The vestibular system contains muscarinic and histamine receptors that, when activated, trigger the vomiting reflex. This pathway explains why motion or changes in head position can induce nausea and vomiting in susceptible individuals.

The solitary tract nucleus (STN) is a neural site in the brainstem that receives signals from gastrointestinal afferent nerves and other sources. It is rich in receptors for enkephalin, histamine, acetylcholine, and serotonin. The STN integrates these signals and communicates with the vomiting center to coordinate the emetic response to various triggers.

The cerebral cortex can initiate vomiting in response to psychological or sensory stimuli such as unpleasant sights, foul smells, or anticipatory stress. This cortical pathway demonstrates that vomiting is not solely a reflex to physical irritants but also responds to higher brain functions and emotional states, explaining stress-related and anticipatory nausea.

Multiple neurotransmitters including serotonin, dopamine, histamine, acetylcholine, and substance P trigger the vomiting reflex by binding receptors in the vomiting center or chemoreceptor trigger zone. Because different triggers activate different receptor pathways, targeting these receptors with antiemetic drugs allows treatment of diverse causes of nausea and vomiting, including chemotherapy-induced nausea and vomiting dopamine receptor antagonists.