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Central neurocircuitry associated with emesis
1Department of Pharmacology, Louisiana State University Health Sciences Center, 1901 Perdido Street, New Orleans, LA 70112, USA.
Insights
Nausea and vomiting involve coordinated neural pathways in the medulla oblongata, not a single "vomiting center." Newer antiemetics target vagal afferents and the dorsal vagal complex for symptom relief.
Area of Science:
- Neuroscience
- Gastroenterology
Background:
- Nausea and emesis are triggered by diverse stimuli including toxins, drugs, and motion.
- Cyclic vomiting syndrome is common in children, highlighting the need for effective treatments.
- Autonomic control of emesis is coordinated in the medulla oblongata.
Purpose of the Study:
- To elucidate the neural circuitry underlying nausea and emesis.
- To understand the mechanisms of action for current and novel antiemetic drugs.
- To identify therapeutic targets for conditions like cyclic vomiting syndrome.
Main Methods:
- Review of neuroanatomical pathways involved in emesis.
- Analysis of the sites of action for various antiemetic agents.
- Examination of the role of the nucleus tractus solitarius (NTS) and central pattern generators (CPGs).
Main Results:
- Emesis coordination involves interconnected neuronal groups in the medulla, not an isolated vomiting center.
- 5-HT(3)-receptor antagonists and neurokinin-1 receptor (NK(1)R) antagonists act on vagal afferents or the dorsal vagal complex.
- Delta(9)-tetrahydrocannabinol (Delta(9)-THC) acts on cannabinoid CB1 receptors in the dorsal vagal complex, affecting gastric motility.
Conclusions:
- Understanding the complex neural network in the medulla is crucial for managing emesis.
- Targeting specific receptors in the dorsal vagal complex and vagal afferents offers effective antiemetic strategies.
- Predicting antiemetic effects of drugs altering motility remains challenging, particularly for delayed emesis and cyclic vomiting syndrome.
Abstract:
Ingestion of toxin, traumatic events, adverse drug reactions, and motion can all result in nausea and emesis. In addition, cyclic vomiting syndrome is quite prevalent in the pediatric population. Coordination of the various autonomic changes associated with emesis occurs at the level of the medulla oblongata of the hindbrain. Chemosensitive receptors detect emetic agents in the blood and relay this information by means of neurons in the area postrema to the adjacent nucleus tractus solitarius (NTS). Abdominal vagal afferents that detect intestinal luminal contents and gastric tone also terminate in the NTS (gelatinosus, commissural, and medial subnuclei). The NTS is viscerotopically organized into subnuclei that subserve diverse functions related to swallowing (subnucleus centralis), gastric sensation (subnucleus gelatinosus), laryngeal and pharyngeal sensation (intermediate and interstitial NTS), baroreceptor function (medial NTS), and respiration (ventrolateral NTS). Neurons from the NTS project to a central pattern generator (CPG), which coordinates the sequence of behaviors during emesis, as well as directly to diverse populations of neurons in the ventral medulla and hypothalamus. Thus, it is critical to realize that there is not an isolated "vomiting center," but rather groups of loosely organized neurons throughout the medulla that may be activated in sequence by a CPG. The newer antiemetic agents appear to block receptors in the peripheral endings of vagal afferents to reduce "perception" of emetic stimuli and/or act in the dorsal vagal complex. A primary site of action of 5-HT(3)-receptor antagonists is by means of the vagal afferents. Neurokinin-1 receptor (NK(1)R) antagonists are antiemetics, because they act at a site in the dorsal vagal complex. Part of their effectiveness may be the result of inhibition of the NK(1)R on vagal motor neurons to prevent fundic relaxation, which is a prodromal event essential for emesis. Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the major psychoactive component of marijuana, can be therapeutically useful as an antiemetic. The site of action of Delta(9)-THC is on cannabinoid CB1 receptors in the dorsal vagal complex. However, it decreases fundic tone and antral motility. It is not easy to predict the potential antiemetic effects of drugs that alter motility. Although antiemetic drugs are available for management of acute chemotherapeutic-induced emesis, few treatments are effective for delayed emesis or cyclic vomiting syndrome.