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CURRENT
OPINION Pathophysiology and treatment of motion sickness
John F. Golding a and Michael A. Gresty b
Purpose of review
Motion sickness remains bothersome in conventional transport and is an emerging hazard in visual
information technologies. Treatment remains unsatisfactory but advances in brain imaging,
neurophysiology, and neuropharmacology may provide insights into more effective drug and behavioural
management. We review these major developments.
Recent findings
Recent progress has been in identifying brain mechanisms and loci associated with motion sickness and
nausea per se. The techniques have included conventional neurophysiology, pathway mapping, and
functional MRI, implicating multiple brain regions including cortex, brainstem, and cerebellum.
Understanding of the environmental and behavioural conditions provocative of and protective against
motion sickness and how vestibular disease may sensitize to motion sickness has increased. The problem of
nauseogenic information technology has emerged as a target for research, motivated by its ubiquitous
applications. Increased understanding of the neurophysiology and brain regions associated with motion
sickness may provide for more effective medication in the future. However, the polysymptomatic nature of
motion sickness, high interindividual variability, and the extensive brain regions involved may preclude a
single, decisive treatment.
Summary
Motion sickness is an emerging hazard in information technologies. Adaptation remains the most effective
countermeasure together with established medications, notably scopolamine and antihistamines.
Neuropharmacological investigations may provide more effective medication in the foreseeable future.
Keywords
motion sickness, neurophysiology, vestibular, virtual reality
A resurgence of interest in motion sickness in recent increased sensitivity to odors [1 ]. The importance
years has been attributable to the use of nauseogenic and negative impact on performance of sopite is
&
visual displays and realization of the involvement of underestimated [2 ], and yawning has been shown
&
the vestibular system, the key mechanism in motion to be a behavioural marker [3 ]. The headache pro-
&&
sickness, with clinical disorders including migraine. voked can be migrainous and disabling [1 ]. Gastric
Nonetheless, characteristic of the history of motion dysrhythmias may provide a marker of nausea in
sickness studies, progress has been slow. Some of the motion sickness [4], and drop in stomach fundus
&
central neuronal pathways involved in processing of and sphincter pressure correlates with nausea [5 ].
provocative stimuli have been identified. There is
greater understanding of the environmental and PROVOCATIVE CIRCUMSTANCES
behavioural circumstances and medical conditions In an extensive survey of a cruise ship, motion sick-
that modulate motion sickness, but little advance ness was the most common reason for physicians’
in treatments.
a
Department of Psychology, University of Westminster and bDivision of
Brain Sciences (Neuro-Otology Unit), Imperial College London, Charing
SYMPTOMATOLOGY Cross Hospital, London, UK
Motion sickness is polysymptomatic. Nausea and Correspondence to Prof John F. Golding, Department of Psychology,
vomiting may be accompanied by a host of signifi- University of Westminster, 309 Regent Street, London W1B 2UW, UK.
cant symptoms including headache, sopite (drows- Tel: +44 2079115000; e-mail: goldinj@westminster.ac.uk
iness), sweating, facial pallor, cold sweating, Curr Opin Neurol 2015, 28:83–88
increased salivation, sensations of bodily warmth, DOI:10.1097/WCO.0000000000000163
1350-7540 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-neurology.com
MS susceptibility 95% CI
***
age self-exposure to circumstances causing disori-
&&
entation or motor instability [1 ]. Recent variants of 60
the last idea postulate that motion sickness evolved
to discourage risky activity in the ancestral fish that 40
were suffering vestibular malfunction [20] or proto-
hominids would avoid looking for food in swaying 20 *
trees that might threaten security, thus tending to **
survive [21]. 0
1350-7540 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-neurology.com 85
Physiological markers for predicting motion motion-induced nausea [39]. Exertion of control
sickness susceptibility have proved elusive. reduced motion sickness induced by playing video
Although motion sickness produces profound auto- games on a tablet computer [40]. Lying supine, or
nomic changes, baseline autonomic characteristics aligning the body with changes in the GIF environ-
are unlikely to provide useful predictors [29]. The ment, or avoiding head movements can reduce
&&
evidence that individual differences in postural motion sickness [1 ]. Consistent with the latter
stability or perceptual style are good predictors of observation, passive restraint of head, shoulders,
motion sickness susceptibility seems limited and hips, and knees reduced motion sickness induced
&& && &
contradictory [1 ,15 ,30 ]. Shorter time constants by playing a video game while standing [41].
of the central vestibular velocity store have been It has long been known that view of a stable
suggested to correlate with reduced motion sickness horizon reference can increase resistance to motion
& &&
susceptibility [30 ], but there is sufficient contrary sickness [1 ] but provision of an artificial horizon
evidence to question if this is a reliable predictor; it failed to have any effect on Mal de debarquement
has been suggested that it is not the duration of the [42]. Standing with a wider stance width and view of
time constant per se, but the ability to modify readily the horizon may reduce postural instability and
&&
the time constant that may be a candidate marker motion sickness at sea [43 ]. Stroboscopic illumi-
&&
for success in motion sickness habituation [1 ]. In a nation protected against motion sickness for back
similar vein, reduced thresholds for cervical vestib- seat military helicopter personnel, perhaps by
&&
ular-evoked myogenic potentials predict future reducing retinal slip [44 ].
habituation to seasickness, the suggestion being Controlled regular breathing has been shown to
that cervical vestibular-evoked myogenic potentials provide increased motion tolerance, and may
at lower thresholds indicates that the individual has involve activation of the known inhibitory reflex
broader dynamic range in which the reflex can between respiration and vomiting [34]. Acupressure
respond and adapt to a wider array of stimulus ampli- bands or electroacupuncture have produced con-
tudes [31]. Individual differences in brain white mat- flicting findings as to their effectiveness against
ter structure revealed by functional MRI may relate to motion sickness [34]. Although galvanic vestibular
nausea susceptibility [32]. Patients with persistent stimulation (GVS) can cause vertigo and nausea, the
Mal de debarquement syndrome exhibit impaired opposite effect has been proposed that it may pro-
postural stability but do not exhibit differences vide a novel, modulatory countermeasure for
in intracortical excitability compared with con- motion sickness [45]. GVS synchronous with the
trols [33]. visual field may normalize electrogastrographic
and autonomic responses and reduce motion sick-
&&
ness during flight simulation [46 ]. Repetitive trans-
BEHAVIOURAL TREATMENTS AND OTHER cranial magnetic stimulation can reduce symptoms
COUNTERMEASURES for Mal de debarquement syndrome [47].
Habituation offers the surest counter measure to Providing pleasant (or unpleasant) scents had
motion sickness being free of side-effects and no effect on motion sickness sensitivity, although
superior to drug treatments but, by definition, is a motion sickness does enhance sensitivity to odors
long-term approach [34]. Optokinetic training gave [48]. Listening to pleasant music can reduce visually
improvements in reducing seasickness in 71% of induced motion sickness [49]. Positive verbal
&
those treated versus 12% of controls [35 ]. Motion instructions and placebo can promote reductions
sickness decreases with repeated exposures to a in motion sickness [50].
high-G flight simulator [36]. More comprehensive
motion sickness desensitization programmes are
highly effective and long-term success rates of PHARMACOLOGICAL
&&
85% have been achieved [37 ]. Visual-vestibuloso- COUNTERMEASURES
matosensory conflict induced by virtual reality Drugs currently used against motion sickness were
&&
increases postural instability and motion sickness- identified over 40 years ago [1 ]. They may be divided
like symptoms. Subsequently, the contribution of into the following categories: antimuscarinics (e.g.,
visual inputs is reduced and such sensory reweight- scopolamine), H1 antihistamines (e.g., dimenhydri-
ing may reflect adaptation to reduce the impact of nate), and sympathomimetics (e.g., amphetamine).
such visually provocative environments [38]. Combinations for example scopolamine and dex-
Being in control, as driver or pilot rather than amphetamine are highly effective since both drugs
being the passenger, affords some protection against combine their different antimotion sickness prop-
&&
motion sickness [1 ]. Similarly, enhanced percep- erties and their respective side-effects of sedation
tions of control and predictability appear to reduce and stimulation cancel each other out. However,
such combinations are less used because of the pharmacotherapeutic research has mainly targeted
abuse potential of amphetamine. The main practi- nausea and vomiting, so far, with little advantage
cal advances have been in drug delivery, such as over established antimotion sickness drugs. Future
the transdermal scopolamine patch to provide development of drugs with highly selective affinities
extended protection but with slow onset, and the to receptor subtypes relevant to motion sickness may
ongoing development of rapid acting intranasal produce an antimotion sickness drug of high efficacy
scopolamine. Other classes of potent antiemetics with few side-effects. However, the polysymptomatic
are not effective against motion sickness, including nature of motion sickness with its high interindivid-
D2 dopamine receptor antagonists and 5HT3 ual variability may preclude a single decisive treat-
antagonists used for side-effects of chemotherapy. ment. In this respect motion sickness is similar to
This is probably because their sites of action may be migraine, with which motion sickness is frequently
at vagal afferent receptors or the brainstem chemo- compounded.
receptor trigger zone, whereas antimotion sickness
&&
drugs act elsewhere [1 ].
Approaches to developing new antimotion sick- Acknowledgements
ness drugs include re-examination of ‘old’ drugs such None.
as phenytoin, as well as the development of newer
agents such as neurokinin1 antagonists. Such drugs Financial support and sponsorship
include phenytoin, betahistine, chlorpheniramine, None.
cetirizine, fexofenadine, benzodiazepines and bar-
biturates, the antipsychotic droperidol, corticoste- Conflicts of interest
roids such as dexamethasone, tamoxifen, opioids
There are no conflicts of interest.
such as the m-opiate receptor agonist loperamide,
neurokinin NK1 receptor antagonists, vasopressin
V1a receptor antagonists, N-methyl-D-aspartate REFERENCES AND RECOMMENDED
antagonists, 3-hydroxypyridine derivatives, 5HT1a READING
receptor agonists such as the antimigraine triptan Papers of particular interest, published within the annual period of review, have
been highlighted as:
rizatriptan, and selective muscarinic M3/M5 receptor & of special interest
antagonists such as zamifenacin and darifenacin && of outstanding interest
&&
[1 ]. So far, none of these drugs have any advantage
1. Golding JF, Gresty MA. Motion sickness and disorientation in vehicles. In:
over those currently available for motion sickness. && Adolfo M, editor. Bronstein Oxford textbook of vertigo and imbalance. Oxford,
The reasons vary and include lack of efficacy and UK: Oxford University Press; 2013. pp. 293–305.
A comprehensive and partially historical review extending to more general dis-
complex pharmacokinetics or, in those that are effec- orientation.
tive, unacceptable side-effects. 2. Lawson BD. MS symptomatology and origins. In: Handbook of virtual en-
Research, however, continues on drug treat- & vironments: design, implementation, and applications. 2nd ed. New York, NY:
CRC Press; 2014; pp. 531–599.
ment. Dexamethasone alleviates motion sickness Highlights significant soporific effect of motion sickness.
in rats in part by enhancing the endocannabinoid 3. Matsangas P, McCauley ME. Yawning as a behavioral marker of mild MS and
& sopite syndrome. Aviat Space Environ Med 2014; 85:658–661.
system [51]. Cannabidiolic acid prevents both Highlights significant soporific effect of motion sickness and possible objective
motion or toxin-induced vomiting in shrews and markers.
4. Koch KL. Gastric dysrhythmias: a potential objective measure of nausea. Exp
nausea-induced behaviour in rats [52]. The relative Brain Res 2014; 232:2553–2561.
effects on semicircular canal and otolith functions 5. Schaub N, Ng K, Kuo P, et al. Gastric and lower esophageal sphincter
& pressures during nausea: a study using visual motion-induced nausea and
by various antimotion sickness drugs including high-resolution manometry. Am J Physiol Gastrointest Liver Physiol 2014;
meclizine, dimenhydrinate combined with cinnar- 306:G741–G747.
Demonstrates the value of modern internal monitoring technique.
izine, and promethazine combined with D-amphet- 6. Schutz L, Zak D, Holmes JF. Pattern of passenger injury and illness
amine may provide insights into their mechanism && on expedition cruise ships to Antarctica. J Travel Med 2014; 21:228–
234.
of action [53]. Ginger (active ingredient gingerol)
A large study that also quantified the relative importance of motion sickness
may have antiemetic effects for motion sickness but compared to other common disorders.
conflicting reports indicate that such effects are 7. Perrin P, Lion A, Bosser G, et al. MS in rally car co-drivers. Aviat Space Environ
Med 2013; 84:473–477.
weak [54]. 8. Clément G, Wood SJ. Eye movements and motion perception during off-
vertical axis rotation after spaceflight. J Vestib Res 2013; 23:13–22.
9. Keshavarz B, Hettinger LJ, Vena D, Campos JL. Combined effects of auditory
and visual cues on the perception of vection. Exp Brain Res 2014;
CONCLUSION 232:827–836.
10. Koslucher FC, Haaland EJ, Stoffregen TA. Body load and the postural
Main advances in recent years have been in identify- precursors of MS. Gait Posture 2014; 39:606–610.
ing brain mechanisms and loci that are associated 11. Naqvi SA, Badruddin N, Malik AS, et al. Does 3D produce more symptoms
& of visually induced MS? Conf Proc IEEE Eng Med Biol Soc 2013;
with motion sickness and/or nausea. Similarly, 2013:6405–6408.
although motion sickness is polysymptomatic, Highlights the implication of new visual technologies for motion sickness.
1350-7540 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved. www.co-neurology.com 87
12. Solimini AG. Are there side effects to watching 3D movies? A prospective 32. Napadow V, Sheehan J, Kim J, et al. Brain white matter microstructure is
& crossover observational study on visually induced MS. PLoS One 2013; 8:e56160. associated with susceptibility to motion-induced nausea. Neurogastroenterol
Highlights the implication of new visual technologies for motion sickness. Motil 2013; 25:448–450.
13. Bos JE, Ledegang WD, Lubeck AJ, Stins JF. Cinerama sickness and postural 33. Clark BC, LePorte A, Clark S, et al. Effects of persistent Mal de debarquement
& instability. Ergonomics 2013; 56:1430–1436. syndrome on balance, psychological traits, and motor cortex excitability. J Clin
Highlights the implication of new visual technologies for motion sickness. Neurosci 2013; 20:446–450.
14. Pölönen M, Järvenpää T, Bilcu B. Stereoscopic 3D entertainment and its 34. Bronstein AM, Golding JF, Gresty MA. Vertigo and dizziness from environ-
& effect on viewing comfort: comparison of children and adults. Appl Ergon mental motion: MS and Drivers’ disorientation. Semin Neurol 2013;
2013; 44:151–160. 33:219–230.
Gives a different appraisal of the impact new visual technologies for motion 35. Ressiot E, Dolz M, Bonne L, Marianowski R. Prospective study on the efficacy
sickness. & of optokinetic training in the treatment of seasickness. Eur Ann Otorhinolar-
15. Diels C, Howarth PA. Frequency characteristics of visually induced MS. Hum yngol Head Neck Dis 2013; 130:263–268.
&& Factors 2013; 55:595–604. Details an effective behavioural therapy with a controlled trial.
Builds on previous work showing the frequency tuning of motion sickness. 36. Newman MC, McCarthy GW, Glaser ST, et al. MS adaptation to Coriolis-
16. Oman CM, Cullen KE. Brainstem processing of vestibular sensory exaffer- inducing head movements in a sustained G flight simulator. Aviat Space
&& ence: implications for MS etiology. Exp Brain Res 2014; 232:2483–2492. Environ Med 2013; 84:104–109.
Synthesis of theory, neurophysiology, and possible identification of the existence of 37. Lucertini M, Verde P, Trivelloni P. Rehabilitation from airsickness in military
the long predicted ‘sensory conflict’ neuron, the ‘Higgs Boson’ of motion sickness && pilots: long-term treatment effectiveness. Aviat Space Environ Med 2013;
research. 84:1196–1200.
17. Yates BJ, Catanzaro MF, Miller DJ, McCall AA. Integration of vestibular and Shows effectiveness of motion sickness desensitization with a long-term follow-up
& emetic gastrointestinal signals that produce nausea and vomiting: potential of success rates.
contributions to motion sickness. Exp Brain Res 2014; 232:2455–2469. 38. Nishiike S, Okazaki S, Watanabe H, et al. The effect of visual-vestibuloso-
Further elucidation of neurophysiological pathways subserving motion sickness in matosensory conflict induced by virtual reality on postural stability in humans. J
an animal model. Med Invest 2013; 60:236–239.
18. Balaban CD, Ogburn SW, Warshafsky SG, et al. Identification of neural networks 39. Levine ME, Stern RM, Koch KL. Enhanced perceptions of control and
& that contribute to MS through principal components analysis of fos labelling predictability reduce motion-induced nausea and gastric dysrhythmia. Exp
induced by galvanic vestibular stimulation. PLoS One 2014; 9:e86730. Brain Res 2014; 232:2675–2684.
Further elucidation of neurophysiological pathways subserving motion sickness in 40. Stoffregen TA, Chen YC, Koslucher FC. Motion control, MS, and the postural
an animal model. dynamics of mobile devices. Exp Brain Res 2014; 232:1389–1397.
19. Napadow V, Sheehan JD, Kim J, et al. The brain circuitry underlying the 41. Chang CH, Pan WW, Chen FC, Stoffregen TA. Console video games,
&& temporal evolution of nausea in humans. Cereb Cortex 2013; 23:806–813. postural activity, and MS during passive restraint. Exp Brain Res 2013;
Elucidation of brain loci associated with nausea in humans. 229:235–242.
20. Thornton WE, Bonato F. Space MS and MS: symptoms and etiology. Aviat 42. Tal D, Wiener G, Shupak A. Mal de debarquement, motion sickness and the
Space Environ Med 2013; 84:716–721. effect of an artificial horizon. J Vestib Res 2014; 24:17–23.
21. Knox GW. MS: an evolutionary and genetic basis for the negative reinforce- 43. Stoffregen TA, Chen FC, Varlet M, et al. Getting your sea legs. PLoS One
ment model. Aviat Space Environ Med 2014; 85:46–49. && 2013; 8:e66949.
22. Horn CC, Meyers K, Oberlies N. Musk shrews selectively bred for MS display An extensive set of experiments in the real-world environment at sea.
&& increased anesthesia-induced vomiting. Physiol Behav 2014; 124:129–137. 44. Webb CM, Estrada A, Athy JR. MS prevention by an 8-Hz stroboscopic
Animal model showing common genetic underpinning of motion sickness and && environment during air transport. Aviat Space Environ Med 2013;