What is the mechanism of vomiting in the area postrema?

Mechanism of Vomiting in the Area Postrema

The area postrema triggers vomiting through a multistep reflex pathway where it functions as a chemoreceptor trigger zone that detects emetic toxins in the blood and cerebrospinal fluid due to its lack of blood-brain barrier, with subsequent activation of the vomiting center in the medulla through serotonergic and dopaminergic pathways.

Anatomical and Physiological Basis

The area postrema is a specialized structure with unique characteristics:

• Located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle 1
• Functions as a circumventricular organ that serves as an interface between brain parenchyma and cerebrospinal fluid 1
• Lacks a specific blood-brain barrier, allowing it to detect emetic toxins in both blood and cerebrospinal fluid 1
• Forms part of the dorsal vagal complex along with the nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus 1
• Characterized by an anastomosed capillary network 2

Vomiting Pathway Activation

The vomiting reflex involves several key steps:

1. Initial Detection: The area postrema detects emetic stimuli through:

   • Direct sensing of blood-borne toxins (due to lack of blood-brain barrier)
   • Monitoring of cerebrospinal fluid contents
   • Receiving signals from vagal afferent nerve fibers 1

2. Neuronal Activation:

   • Neurons in the area postrema increase their firing in response to emetic drugs 1
   • This activation is demonstrated by increased 2-deoxyglucose uptake and c-fos expression 1

3. Signal Transmission:

   • The activated area postrema projects signals to the neighboring nucleus of the solitary tract (NTS) 1
   • The NTS serves as the beginning of a final common pathway for emetic inputs 1

4. Efferent Response:

   • Efferent impulses are sent from the vomiting center to the salivation center, abdominal muscles, respiratory center, and cranial nerves 3
   • This coordinated response results in the physical act of vomiting

Neurotransmitter Systems Involved

The area postrema contains multiple neurotransmitter receptors that mediate the emetic response:

• Serotonin (5-HT3) receptors: Principal neuroreceptors involved in the emetic response 3
• Dopamine receptors: Major mediators of the vomiting reflex 3
• Other receptors: Acetylcholine, corticosteroid, histamine, cannabinoid, opiate, and neurokinin-1 (NK-1) receptors 3

Clinical Significance

Area Postrema Syndrome

Lesions to the area postrema can produce Area Postrema Syndrome (APS), characterized by:

• Intractable nausea
• Vomiting
• Hiccups 2

This syndrome is commonly seen in:

• Neuromyelitis optica spectrum disorders (NMOSD) due to antibodies attacking aquaporin-4 receptors 2
• Rarely in ischemic stroke affecting the area postrema 2

Pharmacological Targeting

Understanding the area postrema's role in vomiting has led to the development of targeted antiemetic medications:

1. Serotonin (5-HT3) Receptor Antagonists:

   • Ondansetron acts by blocking 5-HT3 receptors in the area postrema 4
   • Granisetron selectively antagonizes 5-HT3 receptors in the area postrema and vagal nerve terminals 5

2. Dopamine Antagonists:

   • Phenothiazine compounds (prochlorperazine, trimethobenzamide, promethazine) exert antiemetic action primarily through central antidopaminergic mechanisms in the area postrema 3

3. Other Antiemetics:

   • NK-1 receptor antagonists target neurokinin receptors in the area postrema and vomiting center 6

Clinical Pearls and Pitfalls

• The area postrema is essential for vomiting induced by most emetic drugs but is not required for motion-induced vomiting or vomiting triggered by vagal afferent activation 1
• The role of the area postrema in radiation-induced vomiting remains controversial 1
• The area postrema is cytologically mature by 14 weeks of gestation, but its functions continue to mature during postnatal months 7
• When evaluating patients with unexplained vomiting, consider neuroimaging to assess the area postrema 7
• In patients with suspected area postrema dysfunction, specialized neuropathological assessment may be warranted 7

Understanding the mechanism of vomiting in the area postrema is crucial for developing effective antiemetic strategies and diagnosing conditions that affect this important brain region.