The Neurophysiology and Treatment of Motion Sickness
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Background: Seasickness and travel sickness are classic types of motion illness. Modern simulation systems and virtual reality representations can also induce comparable symptoms. Such manifestations can be alleviated or prevented by various measures.
Methods: This review is based on pertinent publications retrieved by a PubMed search, with special attention to clinical trials and review articles.
Results: Individuals vary in their susceptibility to autonomic symptoms, ranging from fatigue to massive vomiting, induced by passive movement at relatively low frequencies (0.2 to 0.4 Hz) in situations without any visual reference to the horizontal plane. Younger persons and women are considered more susceptible, and twin studies have revealed a genetic component as well. The various types of motion sickness are adequately explained by the intersensory conflict model, incorporating the vestibular, visual, and proprioceptive systems and extended to include consideration of postural instability and asymmetry of the otolith organs. Scopolamine and H1-antihistamines, such as dimenhydrinate and cinnarizine, can be used as pharmacotherapy. The symptoms can also be alleviated by habituation through long exposure or by the diminution of vestibular stimuli.
Conclusion: The various types of motion sickness can be treated with general measures to lessen the intersensory conflict, behavioral changes, and drugs.
The term “motion sickness” (also called “kinetosis”) describes a set of symptoms that occur in association with motion of a person or his or her surroundings, triggering a stress reaction that results in autonomic symptoms. The onset is often insidious, with drowsiness/yawning and reduced alertness, and symptoms progress through cold sweating and pallor, salivation, and occasionally headache, to nausea and vomiting with incapacitation that can be severe (1).
Once the triggering motion ceases, symptoms generally disappear completely within 24 hours.
After reading this article, the reader should:
- Be familiar with the wide array of motion types and patterns that can trigger motion sickness.
- Understand the widely accepted model of the pathogenesis of motion sickness—the sensory conflict model and its extensions.
- Be able to diagnose motion sickness.
- Be familiar with drug and non-drug treatments and know when each is appropriate.
Motion or travel sickness is as old as the various types of motion that cause it, whether on land, in the air, or at sea; sea sickness is the most notorious and in the extreme case can affect as many as 60% of even an experienced crew (2). In any vehicle or ship, it is generally persons being passively transported who are affected most—a fact well explained by the sensory conflict model presented below.
In days of old, those affected were mainly professional seafarers, a few of whom were unable to adapt adequately. Today, however, we see increasing numbers of temporary “seafarers,” not just on cruise ships, but also, for example, in the offshore wind industry, where it is necessary for “landlubber” engineers and technicians to be transported out to the wind parks in small boats. Modern transportation is also producing an increasing number of other trigger situations that are becoming relevant, from motion sickness in the back seat of a car, in a tilting train or an aircraft, to the “space sickness” experienced by astronauts in conditions of weightlessness.
It would appear that about two thirds of travelers have experienced symptoms of motion sickness at least once in a car, especially when in the back seat; half of them have even vomited, which among other things could have implications for the development of self-driving cars (3). In regard to the risk of becoming seasick on board a ship, and as an aid for shipbuilding design to help mitigate it, an ISO standard (IDO 2631) has even been defined, together with principles for the calculation of “motion sickness incidence” (MSI) that make it easier to estimate the expected percentage of persons who will vomit within 2 hours in given sea conditions (4).
And then there is the new phenomenon of “simulator sickness,” where playing complex video games on large screens or using virtual reality (VR) headsets can lead to symptoms surprisingly similar to those of classic seasickness, even though the persons affected are not physically in motion. As early as 1994, in a study of 146 volunteers, 61% of probands developed symptoms of malaise during a 20-min VR immersion period (5).
Young people, especially children between the ages of 6 and 12 years, and women are believed to be more susceptible to motion sickness (6–9, e1), meaning that symptoms induced by computer simulations are particularly significant for this group.
Whatever the scenario that leads to motion sickness, it is nevertheless often necessary for the person affected to carry out active control tasks in fast-moving scenarios and/or on screen. Examples are the driver who has to intervene in a self-driving car, the drone pilot in a complex situation, or the operator of a virtual reality operation system. To ensure that such control tasks are carried out safely, critical issues are whether and when any relevant reductions in alertness and competence occur, and whether these are noticed at all before the symptoms of nausea obtrude.
Early symptoms of incipient motion sickness with reduced alertness are also called “sopite syndrome” (from the Latin sopire, “to lull, to put to sleep”). The term describes a condition of withdrawal with increasing apathy and lethargy (e2), which the person affected may not even notice him- or herself. Few scientific publications exist on sopite syndrome. At the present time, PubMed shows only 16 publications on this subject.
Many people habituate well to kinetogenic situations that at first cause them malaise. However, other affected persons can be unable to habituate adequately. For example, twins often react very similarly, as shown by a 2006 study of monozygotic and dizygotic twins, suggesting the existence of a genetic background (10).
What, now, do the various situations from seasickness to “simulator sickness” have in common, such that predisposed persons can develop a complex of symptoms that range from reduced alertness to discomfort to feeling violently ill with severe vomiting?
This article will first present pathophysiological models of the causes of motion sickness. Next, neurophysiological aspects of nausea and vomiting in motion sickness will be discussed. The complexity of the neurophysiology involved explains why there are so many different approaches to treatment, including habituation exercises and more unconventional methods in addition to medication.
For the presentation of the pathophysiology of the various forms of motion sickness, a selective literature search on PubMed was carried out for the purpose of determining the extent of consensus on the dominant conflict theory model on the basis of the number of high-quality publications (human studies, clinical trials, reviews) found, and also on particular aspects that extend or supplement the model (eBox).
Explanatory models of motion sickness
Vestibular, somatosensory, and visual afferents (eFigure) provide information about body posture and body movements (e3). The three semicircular canals of the vestibular apparatus are stimulated by angular acceleration, while the otolith organs of the vestibular apparatus (saccule and utricle) are stimulated by linear acceleration (including the acceleration of the Earth), because the otolithic membranes are weighed down by a layer of calcium carbonate crystals embedded within them (e3). The position of the head relative to the torso is reported by proprioceptive afferents from the neck muscles and the vertebral column. Visual inputs provide information on the body‘s own motion and/or that of its environment. Proprioceptive afferents from the joints and skeletal musculature transmit the sense of joints movements, joint position, and acceleration. Normally the three sensory channels (vestibular, visual, and proprioceptive) complement each other without contradiction. The afferents are connected to motor centers in the brainstem, which stabilize body position, e.g., through the use of stabilization reactions.
Sensory conflicts are the most current explanation of motion sickness (11–16). These conflicts arise when information from different sensory channels is contradictory or disagrees with expectations (eFigure). Two categories, each with three conflict types, are described in Table 1 (13, 16). Category A contains conflicts between visual and vestibular information. When both sensory systems report motion, but the reports disagree temporospatially, this is a type A1 conflict. An example would be watching the waves from the deck of a lurching ship. With a type A2 conflict, the visual system is reporting motion but the vestibular system is not. Because in this case the body is actually not in motion, this form is also referred to as “pseudo motion sickness” (13). An example is the already mentioned “simulator sickness” experienced by an observer in a stationary travel simulator watching scenes of traveling around a curve (e4). In type A3 conflict, the vestibular system reports motion but the visual system does not. Examples are reading below deck in a swaying ship, or being a back-seat passenger during a bumpy car ride.
Category B sensory conflicts (eFigure, Table 1) are those caused by incongruent afferent information of the vestibular apparatus. These, then, are sensory conflicts between the five sensors (three semicircular canals, two otolith organs) that are active in the two labyrinths and show some frequency specificity. Slow passive motion, with a period between 0.1 and 0.5 Hz, is more likely to lead to nausea and vomiting than oscillating motion at a higher frequency (11). Studies of probands have shown that linear accelerations in vertical and horizontal directions (raising and lowering or laterally translating a closed cabin) with a varying cycle around 0.2 Hz had a particularly kinetogenic effect (17, e5, e6). The signals from the vestibular apparatus during motion of this periodicity are ambiguous (conflict type B), so that translation is sometimes incorrectly interpreted as tipping over (18, 19, e7). It is possible that visceral receptors registering the movements of the viscera are also involved (20, e8). The frequency specificity explains why the slower motion of ships and car journeys often triggers motion sickness where horse riding and riding a mountain bike, as a general rule, do not (11, 13, 21, e7). Optic flow patterns mimicking cyclical to-and-fro motion at a frequency of 0.2 to 0.4 Hz also triggered pseudo motion sickness (22).
A clear type B1 conflict (Table 1) with motion sickness in the form of a vestibular Coriolis reaction also occurs (11–13, 16, 23, 24, e9) when people tilt their head forward and backward while spinning about their own long axis (Lansberg test). With type B2 conflict, the semicircular canals are stimulated but the otolith organs are not. Examples are caloric nystagmus and head movements under conditions of weightlessness—a rare trigger (12, 13). The rare type B3 conflict, in which the otolith organs alone are stimulated under laboratory conditions, e.g., during constant rotation (no stimulation of the semicircular canals) about the long axis of the body when horizontal (so-called “barbecue rotation”) (e10). Sensory conflicts with proprioception are less important (11–16).
Apart from the sensory conflict (or mismatch) theory, there is also the concept of postural instability (25, e11). This emphasizes the role of the motor system and postulates that the main element leading to motion sickness is inefficient postural control that has not yet adapted to the situation. According to another hypothesis, asymmetry between the bilateral otolith organs favors the occurrence of “space sickness” in astronauts (e12).
Explanatory hypotheses like these add to the sensory conflict theory without invalidating it. The latter has become widely accepted, with a PubMed literature search identifying a correspondingly large number of reviews and clinical trials devoted to it as the main factor (eBox).
Habituation is an important element in motion sickness (11–16). Just as sea sickness often moderates after a few days as the sufferer becomes accustomed to the swaying of the ship, so the converse can happen, although quite rarely: that going ashore after a long voyage can lead to an impaired ability to “switch back” again or “reset,” also known as “mal de débarquement syndrome” or “unsteadiness syndrome.”
Neurophysiologic aspects of nausea and vomiting in motion sickness
Afferents from the vestibular apparatus are involved in all relevant/significant sensory conflicts (Table 1), even those in which it is absence of these signals that leads to the mismatch (type A2 conflict, pseudo motion sickness). Patients with bilateral vestibular failure do not get seasick, neither do they develop pseudo motion sickness (26). The afferents from the labyrinth arrive at the vestibular nuclei of the brainstem, which also receive visual and proprioceptive input and are connected with the vestibulocerebellum (27).
The activity of the vestibular nuclei is influenced by numerous transmitters including acetylcholine, dopamine, γ-aminobutyric acid (GABA), glutamate, glycine, histamine, norepinephrine, and serotonin (24). Efferent projections of these nuclei to the reticular formation, the spinal cord, and the oculomotor nuclei serve the postural motor and the oculomotor systems. Ascending projections from the nuclei reach the temporoparietal cortex areas and insular cortex via the posterolateral thalamus (28). Autonomic reactions can be triggered via connections to the hypothalamus, the nucleus tractus solitarii (NTS), the locus ceruleus, and other nuclei of the reticular formation (including the nucleus parabrachialis).
Recent studies have described brain activity in pseudo motion sickness (29, e13). Probands lying in an MRI scanner were shown a moving pattern of stripes that resulted in the sensation of apparent motion (vection) and in about half the probands led to nausea. The onset of nausea coincided with activity in the amygdala, putamen, and dorsal pons; stronger persistent nausea was accompanied by activity in a variety of cortical areas (insular cortex, cingulate and prefrontal cortex, premotor cortex). Brain areas that react selectively to sensory conflicts alone have not yet been identified, however.
Vomiting due to motion sickness can also take place without involving the higher brain areas, however, as animal studies have shown (15, 30). The core area of interest is a network of brainstem regions often referred to for simplicity as the vomiting center. Various inputs from the vestibular nuclei, the area postrema, the gastrointestinal tract, and other nuclei of the reticular formation all converge at a central “switchboard,” the nucleus tractus solitarii. This means that the NTS can be excited by different stimuli such as toxins in the blood, sensory conflicts, or gastrointestinal symptoms, and this results in activation of adjacent areas of the brainstem and thus finally to vomiting.
The biogenic amine histamine is believed to contribute to the triggering of vomiting in sea sickness (31, e14). Animal studies have shown a direct correlation between sea sickness and histamine metabolism (32, e15). After excessive motion, increased histamine concentrations were shown in the inner ear and brain of the animals studied. This is underscored by experiences with sea sickness, where food with a strong histamine content appears to aggravate symptoms (33).
Diagnosis and treatment strategies in motion sickness
Motion sickness can usually be diagnosed on the basis of the characteristic history of a triggering situation and appropriate differential diagnosis (in accordance with guidelines) to rule out other diseases most of which are otorhinolaryngological or neurological, such as Menière’s disease, certain forms of migraine, or psychological causes (34, e16). In addition to these, however, because of the complex pathophysiology of motion sickness, gastroenterological and infectious diseases and any possible orthopedic causes should also be included in the differential diagnosis. Besides these, visual or cardiovascular disorders such as hypotension or hypoglycemia can also trigger symptoms similar to those of motion sickness (e17). Singh et al. provide an up-to-date overview of the causes of nausea and vomiting (35).
The sensory conflict theory is regarded as the best candidate construct of the pathophysiology of motion sickness, and involves complex neurophysiologic signaling with numerous brain nuclear regions and neurotransmitters participating in the production of the symptoms before the “homestretch” of vomiting is reached. Understandably, therefore, approaches to palliating or treating this “disorder” are similarly varied (Table 2).
Looking in a vehicle’s direction of travel or focusing on the horizon are simple measures that are well known to avoid or at least palliate the symptoms of motion sickness, most likely by reducing intersensory conflict (36). Lying down and reducing visual influences can also have a positive effect. One approach to treatment along similar lines which may perhaps also prove useful against sea sickness is the head-mounted display providing an artificial horizon or horizon information (2, e18–e20).
Another approach is to try appropriate measures to improve habituation to motion stimuli. Such measures include desensitizing physiotherapy (reactive motion and body positioning exercises [e21, e22]) and practicing actively synchronizing body movements with the motion, including tilting the head into turns (36).
Some centers offer specialized habituation training before the start of a sea voyage for patients who suffer from sea sickness (37). This can include optokinetic desensitization over a period of weeks, plus simulated sea motion (swell) and balance training. As a general principle, habituation training attempts to reproduce the disturbing motion pattern as accurately as possible. Repeated exposure training can induce adequate habituation lasting for months, as described in detail by Zhang et al. (38).
Positive effects seem also to have been achieved by the application of transcutaneous electrical nerve stimulation (TENS) and by general stress-reduction measures such as pleasant music or odors (e23–e26).
However, it must be pointed out at this stage that for many of the non-drug interventions in particular, too few prospective controlled clinical studies have yet been carried out for a judgment on their true efficacy to be made; one study dating from 1990 on acupressure bands (“SeaBand”) to prevent sea sickness did not show a positive effect, although P6 point stimulation has been shown to be effective against postoperative vomiting (e27, e28).
It is also important to mention that several recent clinical studies have shown considerable positive placebo effects of drug and non-drug interventions on symptoms of motion sickness (e29–e31). On the one hand this makes it harder to assess the true efficacy of individual treatments, but on the other hand it can also be employed to beneficial effect.
Finally, especially at sea, avoiding foods with a high histamine content, such as tuna, some kinds of cheese, salami, sauerkraut, and red wine (foods/drinks altered by microorganisms) is one of the non-drug interventions or preventive measures (33).
The various forms of drug therapy (Table 3) are based primarily on the role of histamine, referred to above, in the pathophysiology of sea sickness, and on the importance of muscarinic receptors in the vestibular apparatus and vomiting center. Preparations containing antihistamines and anticholinergic drugs are both important here. An example of a monodrug is dimenhydrinate, which dissociates in the blood to diphenhydramine and 8-chlorotheophylline. Dimenhydrinate is often prescribed in combination with cinnarizine for short-term acute therapy. This H1-antagonist acts additionally as a dopamine, serotonin, and bradykinin receptor antagonist and as a calcium inhibitor. This is believed to result in synergistic effects in the vestibular apparatus. Typical adverse effects of the antihistaminergic properties of dimenhydrinate alone or in combination with cinnarizine are fatigue, slowed reactions, and impaired coordination and concentration. The incidence of adverse effects varies greatly in prospective studies and has been estimated at about 5% (e32–e35); the duration of action when taken orally is 4–8 hours.
In a prospective study of patients with vestibular disorders, the response rate to a combination of dimenhydrinate and cinnarizine was 78%, whereas when these drugs taken separately the rates were only 45% and 55% respectively (e33). Anticholinergics in the form of transdermal scopolamine patches (TTS-S, transdermal therapeutic system—scopolamine) are also often used (38). The patches have a duration of action of up to 3 days and are used both preventively and for long-term therapy.
There are no prospective randomized studies on the effect of this treatment on motion sickness, nor any valid comparative studies with other drugs. However, the authors of a Cochrane review conclude that the effect of scopolamine is not superior to that of antihistamines or combination drugs, but it does have fewer adverse effects (39). The adverse effects derive from its anticholinergic properties and include, especially, mucosal dryness and mydriasis, palpitations, urinary retention, and, very rarely, hallucinogenic effects (e36). All of these substances have in common that they do not totally prevent or suppress sea sickness, for example, but they can greatly ameliorate symptoms. This comes at a cost, however, of adverse effects that can impair alertness and thus represent a safety risk for many tasks, e.g., on board a ship (19, 23).
Apart from these drug therapies, natural remedies are also used to suppress sea sickness. There are indications, even including a prospective, placebo-controlled study of sea cadets, showing that ginger can be used as an antiemetic with few adverse effects (40, e37, e38). The substances it contains are believed to act as antagonists at the 5-HT3 receptor, which has an important role in the vomiting center.
High-dose vitamin C, another remedy which has been credited with some antihistaminergic effect, was shown in a prospective, double-blind, placebo-controlled study to reduce the symptoms of sea sickness without identifiable adverse effects (31).
The dopamine antagonist metoclopramide is not indicated for the treatment of motion sickness. Metoclopramide can cause extrapyramidal symptoms in children and adolescents and/or when given at high doses, and if given over long periods, especially in older patients, can trigger tardive dyskinesia that can sometimes be irreversible. For this reason, metoclopramide may be used only for the prevention of delayed nausea and vomiting after chemo- and radiotherapy or for symptomatic treatment of nausea and vomiting due to acute migraine (and not in children or adolescents). Particularly effective antiemetics such as the 5-HT3 antagonist ondansetron or the neurokinin-1 antagonist aprepitant are also contraindicated for the treatment of motion sickness. Ondansetron can very often cause headache and sometimes seizures, extrapyramidal symptoms, and constipation, among other effects. Aprepitant often causes headache, constipation, and other adverse effects which may appear acceptable in the context of weighing risks against benefits during a highly emetogenic form of chemotherapy, but are unacceptable in the context of preventing motion sickness.
The explanatory model of sensory conflicts involving primarily the visual, vestibular, and proprioceptive systems describes how motion sickness arises in a range of forms, from classic sea sickness to “simulator sickness” in modern virtual reality systems. The symptoms can vary greatly, ranging from reduced alertness (sopite syndrome) to full-blown severe vomiting. The importance of sopite syndrome and how to measure it objectively is the subject of ongoing research.
Reflecting the complexity of the central nucleus areas and neurotransmitters involved in the development of the symptoms of motion sickness, options for treatment include a number of approaches that differ greatly from each other but may nevertheless achieve success. They range from drug treatment, tried and tested and based mainly on H1-antihistamines and anticholinergics, to symptom relief with vitamin C and ginger, to a multiplicity of behavioral measures aimed at desensitizing or improving habituation by means of physiotherapeutic exercises or habituation to stimuli that trigger motion sickness.
Given the increasing relevance of sensory conflicts, not just in faster moving vehicles, but in digitally processed environments, in some of which full alertness is still absolutely essential, it would seem that continued development of drug options with fewer adverse effects is required.
The term “motion sickness” describes a set of autonomic symptoms caused by incongruent sensory impressions under conditions of motion. Cold sweats, pallor, nausea, and vomiting are caused by a stress reaction to the motion.
Young people, especially children between the ages of 6 and 12 years, and women are believed to be more susceptible to motion sickness.
Twins often react very similarly, as shown by a 2006 study of monozygotic and dizygotic twins, suggesting the existence of a genetic background.
The sensory conflict model is widely accepted as explaining the pathogenesis of motion sickness. Incongruent sensory information results in conflict between the vestibular, optic, and proprioceptive systems.
Type A conflict
Type A sensory conflicts are caused by incongruent afferent information from the vestibular and visual sensory organs.
Type B conflict
Incongruence between information from the semicircular canals and the otolith organs produces type B conflict.
Development of symptoms involves complex central brain structures and nuclear regions with many neurotransmitters participating, including histamine.
Motion sickness is diagnosed on the basis of a history of a triggering situation and exclusion of neurologic, otorhinolaryngologic, gastroenterologic, and infectious diseases and orthopedic causes.
Various non-drug interventions relieve the symptoms of motion sickness, by, for instance, reducing sensory conflict.
Anticholinergics are used for prevention, e.g., transdermal scopolamine. Administration should be 6 to 8 h before travel starts or before the expected onset of motion sickness.
Apart from a number of non-drug interventions, H1-antihistamines with the lowest possible potential for sedation are the main treatment of choice for vertigo, nausea, and vomiting due to motion sickness.
Because of severe adverse effects, the use of metoclopramide, ondansetron, or aprepitant to prevent or treat motion sickness is contraindicated.
The development of vehicles without constant outside view, and of virtual reality environments, requires drug options with fewer adverse effects.
Conflict of interest statement
The authors declare that no conflict of interest exists.
Manuscript received on 28 March 2018, revised version accepted on
9 August 2018
Translated from the original German by Kersti Wagstaff, MA
Prof. Dr. med. Andreas Koch
Schifffahrtmedizinisches Institut der Marine,
24119 Kronshagen, Germany
Sektion Maritime Medizin am Institut für Experimentelle Medizin
der Christian-Albrechts-Universität zu Kiel
For eReferences please refer to:
eBox and eFigure:
Institute of Experimental Medicine, Section Maritime Medicine Christian-Albrechts-Universität, Kiel: Prof. Dr. med. Andreas Koch, Dr. med. Sebastian Klapa
Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Campus Kiel: Prof. Dr. med. Dr. rer. nat. Ingolf Cascorbi
Clinic for Otorhinolaryngology and Plastic Surgery of the Head and Throat, RWTH Aachen: Prof. Dr. med. Martin Westhofen
Department of Neurology, RWTH Aachen: PD Dr. med. Manuel Dafotakis
Institute of Physiology Christian-Albrechts-University, Kiel:
Prof. Dr. med. Johann Peter Kuhtz-Buschbeck
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