Nausea is an unpleasant feeling, usually located in the stomach or upper abdomen, that often comes with a strong urge to vomit. Clinicians treat it as a symptom rather than a disease in its own right: it causes an uncomfortable feeling in the stomach and a strong urge to vomit. It is among the most common complaints in both outpatient and inpatient medical settings, and it overlaps closely with vomiting, the forcible expulsion of stomach contents. The two symptoms are often grouped together as "nausea and vomiting" (N/V), but they can occur separately.
Nausea and vomiting as distinct symptoms
Nausea and vomiting are related but not identical. Nausea may occur on its own or along with vomiting, dizziness or stomach pain. Vomiting is the more visible endpoint of a reflex, while nausea is a subjective sensation that may or may not progress to emesis. Some drugs and conditions relieve one symptom much more effectively than the other, a point that shapes treatment choices (see below).
Physiology
Nausea and vomiting are generally understood as the outcome of continuous interactions between the gastrointestinal tract, including its enteric nervous system, the CNS, and the autonomic nervous system. The physiology is incompletely understood, but several anatomical sites and neurotransmitter systems have been identified.
Brainstem control
Vomiting is coordinated in the brainstem. The efferent neurons that produce the vomiting response are organised by a region in the medulla oblongata, on the floor of the fourth ventricle. Earlier models described a discrete "vomiting centre," but this view has been revised. One review notes that Miller and Wilson could not identify any discrete locus and concluded that the neural circuitry involved in emetic responses is diffusely distributed. For this reason some authors propose the term "emetic complex" for loosely organised groups of neurons that are activated in sequence.
The blood–brain barrier-free chemoreceptor trigger zone (CTZ), located in the area postrema on the floor of the fourth ventricle, is a key entry point for chemical stimuli. Because it sits outside the blood-brain barrier, detecting stimuli in the blood and cerebrospinal fluid, circulating toxins and many drugs can act on it directly. This is also why many antiemetic drugs target the CTZ.
Afferent inputs
Signals reach the brainstem from several directions:
- Vestibular system. Changes in head position can trigger nausea through the inner ear's balance apparatus, which explains motion sickness. Changes in head position can stimulate the central nervous system to produce nausea and vomiting through input from the vestibular system in the inner ear.
- Gastrointestinal tract. Vagal and spinal afferent nerves respond to mucosal irritation. Chemotherapy, radiation, distension, or gastroenteritis can cause serotonin release and stimulate CTZ and the vomiting center.
- Cerebral cortex. Sensory input, anxiety, meningeal irritation and raised intracranial pressure can all contribute to nausea through higher brain areas. The cerebral cortex contributes to nausea by the direct input from the 5 senses, as well as by anxiety, meningeal irritation, and increased intracranial pressure.
- Other stimuli. Visual, gustatory, olfactory and painful stimuli, as well as low blood pressure and low oxygen levels, can send signals to the nucleus tractus solitarius (NTS) in the brainstem.
Neurochemistry
Several neurotransmitters and receptors are involved. One review lists histamine (H_1 receptors), dopamine (D_2), serotonin (5-HT_3), acetyl choline (muscarinic) and neurokinin (substance P). Substance P is particularly relevant to the final common pathway: it is present in high concentrations in the vomiting centre, and it appears to participate in the pathways leading to emesis. Drugs that block these receptors form the basis of most pharmacological treatment.
Causes
Nausea has a broad range of causes, and multiple factors often simultaneously cause nausea and vomiting. Common categories include:
- Infections. These range from generalized (sepsis, pneumonia, coronavirus) or more localized infectious processes (viral gastroenteritis, cholecystitis, bacterial peritonitis, clostridium difficile).
- Medications and toxins. Drug effects are considered a leading cause. Frequent culprits include antibiotics; opioid-induced nausea (OIN); chemotherapy induced nausea and vomiting (CINV); antidepressants.
- Cancer and its treatment. Some types of cancer and cancer treatments can cause nausea and vomiting, including radiation to the upper body and chemotherapy. Among patients with advanced disease, opioid-related nausea is especially common; one source reports it in up to 40% of patients with advanced cancer.
- Pregnancy. Hormonal changes in the first trimester are a well-known cause. The severe form, hyperemesis gravidarum, occurs in 0.3–3% of pregnancies and is defined by significant weight loss and electrolyte disturbance.
- Vestibular and neurological conditions. Balance disorders, migraine and conditions that raise pressure inside the skull can all produce nausea.
- Gastrointestinal and metabolic conditions. These include gastritis, ulcers, gallbladder disease, bowel obstruction, and endocrine or metabolic disorders.
- Psychogenic factors. Stress and anxiety are recognised contributors, and anxiety disorders are associated with chronic symptoms.
- Postoperative nausea. Surgical patients are frequently affected, partly because of anaesthetic agents and opioids.
Clinical assessment
Evaluation usually starts with a careful history. One approach in the clinical literature involves defining what the patient means by the symptom, determining whether it is acute or chronic, considering medication or toxin effects, forming a differential diagnosis, and then selecting treatment based on the neurotransmitters involved. Diagnostic steps often include a review of recent illness, diet and medications, a physical exam focusing on the abdomen and hydration, and laboratory tests for infection, dehydration or metabolic abnormalities. Imaging is used when an abdominal condition is suspected. Acute or mild symptoms are often managed with an empirical trial of antiemetics without extensive testing.
Persistent nausea can have serious consequences. It can lead to issues like dehydration, malnutrition and unexpected weight loss, and in cancer patients it affects both physical and psychological well-being.
Management
Lifestyle and self-care
For mild nausea, simple measures are commonly recommended. These include small, frequent meals to allow the stomach to digest foods gradually, bland foods, and avoidance of known triggers. Some people find ginger helpful; alternative therapies like acupuncture and ginger may help some patients. Clear liquids help prevent dehydration when vomiting accompanies nausea.
Pharmacological treatment
Antiemetic drugs act on the receptor systems described above. Commonly used classes include antihistamines; dopamine antagonists; serotonin antagonists; neurokinin antagonists; anticholinergics; benzodiazepines; corticosteroids. Antihistamines such as meclizine are often used for motion sickness, and scopolamine patches are another option. Certain prescription agents, including ondansetron, are widely used for chemotherapy-related symptoms.
A key limitation is that the drugs most effective against vomiting are not always the best for nausea. Newer 5-HT3 and NK1 receptor antagonists while being very effective for vomiting, are less satisfactory for the management of nausea. Evidence for individual agents in acute settings is also mixed: a 2015 Cochrane review of eight trials in emergency care found no definitive evidence to support the superiority of one drug over another.
Other approaches
Non-pharmacological options under study include bio-electrical stimulation of the gastrointestinal tract, behavioral training and newer surgical therapies. Medical cannabis is also used for some patients, though its legal status varies by location.
Special situations
Severe pregnancy-related nausea often requires hospital care. Intravenous fluids and vitamin supplementation are usually necessary, and thiamine is added to prevent Wernicke's encephalopathy.
Open questions
Despite its prevalence, nausea is less well understood than vomiting. One physiology review noted that the physiology is poorly understood, which limits the development of targeted drugs. Because nausea responds less reliably to existing antiemetics, research continues into the neural circuits and cellular signalling that distinguish the subjective sensation from the reflex itself.
References
- Nausea Causes, Symptoms and Relief Optionsriversideonline.com
- Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systemsncbi.nlm.nih.gov
- Pathophysiology of nausea and vomiting in palliative medicine - Smith - Annals of Palliative Medicineapm.amegroups.org
- Pathophysiology of Vomitingjove.com
- Molecular and Circuit Mechanisms Regulating Nausea and Vomiting: Recent Advances and Future Perspectivesscienceopen.com
- Module: Nausea and Vomitingfacs.org
- Physiology and pharmacology of nausea and vomiting - ScienceDirectsciencedirect.com
- Vomiting Mechanismnews-medical.net
- Nursing Support for Nausea and Vomiting in Patients With Cancer: A Scoping Reviewncbi.nlm.nih.gov
- Nausea and Vomiting: Common Etiologies and Managementmypcnow.org
- Nausea and vomiting: Causes, treatments, and tipsmedicalnewstoday.com
- Review of NVP and HG and Early Pharmacotherapeutic Interventionncbi.nlm.nih.gov
- Nausea (Feeling Sick or Nauseous ) Causes & Treatmentmy.clevelandclinic.org
- Nausea Guide: Causes, Symptoms and Treatment Optionsdrugs.com
- Nausea and Vomiting in 2021: A Comprehensive Update - PMCpmc.ncbi.nlm.nih.gov
- Vomiting: Physiology of vomitinggpnotebook.com
- Peripheral Nervous Pathways Involved in Nausea and Vomitinglink.springer.com
- A Practical 5-Step Approach to Nausea and Vomiting - Mayo Clinic Proceedingsmayoclinicproceedings.org