Vestibular function and space motion sickness

The vestibular system plays an important role in intersensory interactions and gravitation is a natural stimulus for its receptors. Weightlessness alters the input signals of the otoliths and their effect on the pattern and dynamics of changes in the vestibular function (VF), which is accompanied by development of space adaptation syndrome (SAS) and space motion sickness (SMS). These changes occur both during the spaceflight (SF) and after returning to Earth, but the mechanisms of their development are still poorly understood and require special studies. In total, 47 Russian cosmonauts (crewmembers of long-term International Space Station (ISS) missions) have participated in the studies into VF before and after SF and nine of them, in onboard studies during SF (129–215 days) as a part of the Virtual space experiment (stage 1). Electro- and video-oculography are used to record spontaneous eye movements (SpEM), static vestibular–ocular responses during head tilts to the right or left shoulder (static otolith–cervical–ocular reflex, OCOR), and dynamic vestibular-ocular response during the head rotation around the longitudinal axis of the body. The examination is accompanied by personal and questionnaire survey on subjective responses and complaints of cosmonauts about SAS and SMS. Significant changes in SpEM (drifts of eyes, spontaneous and gaze-evoked nystagmus, and arbitrary saccades) and a decrease in OCOR (statistically significant decrease in the amplitude of ocular counter-rolling in response to head tilts up to its absence or inversion, an atypical OCOR) are observed during SF. An atypical OCOR is observed at the beginning of adaptation to weightlessness in seven of the nine cosmonauts (the first one to two weeks of SF) and repeatedly throughout the flight in all cosmonauts regardless of whether it is their first flight or not. Atypical vestibular responses after SF, similar to the responses during SF, are observed in several cosmonauts by day 9 after flight. It has been shown that atypical OCOR variants are more frequently observed in the subjects lacking any previous space experience, as well as a more pronounced decrease in this response with a concurrent increase in the response of the semicircular canals. It is also demonstrated that repeated SFs lead to a considerable shortening in the after-flight readaptation to terrestrial conditions and a considerable decrease in the degree of vestibular disorders. In the initial period of SF, the changes in VF are correlated with the complaints and manifestations of SAS and SMS; however, the complaints and the corresponding symptoms are unobservable during the further flight despite significant changes in the VF state. The patterns of the VF disorders associated with the impact of weightlessness and observed during and after SF are very similar, allowing these disorders to be regarded as SAS and SMS of different severities (intensities).     

Suncus murinus as a new experimental model for motion sickness

Characteristics of motion sickness and effects of possible prophylactic drugs were studied using Suncus murinus (house musk shrew) for its potential use as an experimental model in motion sickness. Mild reciprocal shaking (amplitude: 10-40 mm; frequency: 0.5-3.0 Hz) induced vomiting in most of Suncus murinus within 2 min. Adaptation was observed when the motion stimulus was repeated with an interval of 2 to 3 days. During the repetitive motion training, both the ratio of sensitive animals and the number of vomiting episodes decreased, and the time from the start of shaking to the first vomiting was extended. Subcutaneous injection of scopolamine (100 mg/kg), chlorpromazine (8 mg/kg), promethazine (50 mg/kg), diphenhydramine (20 mg/kg), chlorphenylamine (20 mg/kg) and methamphetamine (2 mg/kg) decreased the emetic effect of motion sickness, but pyrilamine (20 mg/kg), meclizine (20 mg/kg) and dimenhydrinate (32 mg/kg) were not effective or very weak. These results indicate that the Suncus murinus is sensitive to the motion stimulus and antiemetic drugs are effective as prophylaxis. The Suncus murinus is useful as a new experimental animal model for motion sickness.     

Asynchrony of labyrinthine receptors as a physical factor in motion sickness

Evidence is presented to show that despite their effectiveness in producing motion sickness the actual frequencies and accelerations involved in ship motion are rather low. It is suggested that the disparity is due to the fact that ship motion is such as to cause an asynchrony between signals from the labyrinth and those from other motion receptors.     

Gravitation biology using fish as model systems for understanding motion sickness susceptibility

During the entire evolution of life on Earth, the development of all organisms took place under constant gravity conditions, against which they achieved specific countermeasures for compensation and adaptation. On this background, it is still an open question to which extent altered gravity such as hyper- or microgravity (centrifuge/spaceflight) affects the normal individual development, either on the systemic level of the whole organism or on the level of individual organs or even single cells. The present short review provides information on this topic, focusing on the effects of altered gravity on developing fish as model systems even for higher vertebrates including humans, with special emphasis on the effect of altered gravity on behaviour and particularly on the developing brain and vestibular system.     

The dead space in a compartmental lung model

A compartmental lung model with any number of synchronously filling and emptying functional chambers and a common dead space or conducting region is considered. It is shown that the model gives rise to an output, in an open circuit washout determination, which is a weighted sum of exponentials. From estimates of these weights and exponential components, estimates of the model parameters can be recovered. Relations giving the unique correspondence between the output parameters and the model parameters are derived and the existence and uniqueness of solutions established.     

Altered susceptibility to motion sickness as a function of subgravity level

Large interindividual differences among 74 normal subjects in the change in susceptibility to motion sickness with effective lifting of the normal g-load by parabolic flight maneuvers were recorded with high test-retest reliability. Most subjects, who were required to make standardized head movements while seated in a chair rotating at a constant speed, demonstrated either a substantial increase or a decrease in susceptibility, in confirmation of a previous study, while a few appeared to be more or less unaffected by the 1 g to 0 g gravitational change. A similar test procedure conducted with eighteen of the subjects at lunar- and Martian-gravity levels revealed further interindividual differences in susceptibility as a function of g-level. The subjects with gravity-dependent susceptibility revealed: (1) a progressive change in susceptibility as a function of g-load in either the positive or negative direction that was characteristic of the individual, (2) a susceptibility level that appeared to be maintained at the fractional g-load, and (3) immunity to motion sickness at all g-levels tested below the Earth standard. The case history as well as ground-based functional and provocative tests of normal subjects proved to be inadequate in predicting susceptibility to motion sickness under subgravity conditions.This research was conducted under the sponsorship of the Biomedical Research Office, Order T-81633, Manned Spacecraft Center, and the Office of Life Sciences, NASA, Washington, D. C., Order L-43518. Opinions or conclusions contained in this report are those of the authors and do not necessarily reflect the views and endorsement of the Navy Department.     

Susceptibility to motion sickness in fish: a parabolic aircraft flight study

Juvenile swordtail fish and larval cichlids were subjected to parabolic aircraft flights (PAFs) and individually observed. After the PAFs, inner ear otoliths and sensory epithelia were examined on the light microscopical level. Otolith asymmetry (differences in otolith size between the left and the right side) was especially pronounced in those fish, who exhibited a kinetotic behaviour (e.g., spinning movements) during microgravity. This speaks in favour of a theoretical concept according to which susceptibility to space motion sickness in humans may be based on asymmetric inner ear stones. The cell density of sensory epithelia was lower in kinetotic animals as compared to normally swimming fish. Thus, asymmetric otoliths can cause kinetosis in fish during PAFs, but susceptibility to kinetosis may also be based on an aberrative inner ear morphology.     

Transmission and control of African horse sickness in The Netherlands: a model analysis

African horse sickness (AHS) is an equine viral disease that is spread by Culicoides spp. Since the closely related disease bluetongue established itself in The Netherlands in 2006, AHS is considered a potential threat for the Dutch horse population. A vector-host model that incorporates the current knowledge of the infection biology is used to explore the effect of different parameters on whether and how the disease will spread, and to assess the effect of control measures. The time of introduction is an important determinant whether and how the disease will spread, depending on temperature and vector season. Given an introduction in the most favourable and constant circumstances, our results identify the vector-to-host ratio as the most important factor, because of its high variability over the country. Furthermore, a higher temperature accelerates the epidemic, while a higher horse density increases the extent of the epidemic. Due to the short infectious period in horses, the obvious clinical signs and the presence of non-susceptible hosts, AHS is expected to invade and spread less easily than bluetongue. Moreover, detection is presumed to be earlier, which allows control measures to be targeted towards elimination of infection sources. We argue that recommended control measures are euthanasia of infected horses with severe clinical signs and vector control in infected herds, protecting horses from midge bites in neighbouring herds, and (prioritized) vaccination of herds farther away, provided that transport regulations are strictly applied. The largest lack of knowledge is the competence and host preference of the different Culicoides species present in temperate regions.     

Comparison of various motion stimuli on motion sickness and acquisition of adaptation in Suncus Murinus

Effects of various types of motion stimuli were compared to investigate optimum method to elicit motion sickness and adaptation in Suncus murinus (suncus). Three different direction of shaking in the horizontal plane, back and forth, right and left and revolving, induced emetic response to the similar extent. However, vertical shaking was far less effective in inducing motion sickness. Mild and severe horizontal shaking (15 min per day) was continued for 14 days and emetic response to standard motion stimulus was compared before and after the training. The severe daily acceleration strongly depressed the susceptibility to motion stimulus. The mild acceleration which was not emetic stimulus in itself also remarkably attenuated the vomiting response to standard motion stimulus. These results indicate that 1) the emetic responsiveness of the suncus does not depend on the modes of shaking as long as the direction is in the horizontal plane, 2) the suncus is relatively refractory to the vertical linear acceleration and 3) the adaptation to motion stimulus does not develop on the latest peripheral steps of the vomiting reflex pathways.     

A sustained hyper-g load as a tool to simulate space sickness

In April 1989 the three European scientist astronauts of the D1 Spacelab Mission were exposed to a 1.5 hours +3G centrifuge run in supine position, resulting in a linear acceleration along the subjects' x-axis. Afterwards, severe motion sickness symptoms were provoked by head movements (Sickness Induced by Centrifugation: SIC). The astronauts mentioned close similarities with what they experienced in space during the D1-Spacelab Mission in 1985, where head movements also provoked motion sickness symptoms (Space Adaptation Syndrome: SAS). Moreover, the astronauts agreed that the rank order of their susceptibility to SAS was the same as for SIC. It was therefore postulated that with this method SAS could be simulated on earth. Additionally, in otolith function tests following the centrifuge run, changes in visual-vestibular interaction were observed, which replicated objective findings obtained with the same astronauts immediately after the D1 Spacelab Mission. During the last couple of years a series of experiments has been carried out to determine the nature of the stimulus causing SIC, the incidence of SIC, and the underlying cardio-vascular and/or vestibular mechanisms. These experiments were carried out on several astronauts and some 50 'normal' healthy subjects. In the next sections the main findings of all these experiments and the implications are summarized.     

Factors influencing the susceptibility of anurans to motion sickness

We examined the propensity for motion sickness in five anuran species, concentrating our efforts on the treefrog Rhacophorus schlegelii, because it had shown the greatest susceptibility to motion sickness in a previous study. We used parabolic flight as our provocative stimulus and fed all specimens a known volume of food 1.5-3 h before flight. The presence of vomitus in a frog's cage was our indicator of motion sickness. Significantly more emesis was observed in flight-exposed than in control R. schlegelii (P < 0.05). There was no sex difference in susceptibility to motion sickness (P > 0.5). Individuals that vomited were significantly larger (P < 0.02) than those that did not. Among microgravity-treated frogs, those that vomited spent on average 85% more time airborne and tumbling in microgravity than those that did not vomit (P=0.031). Our data support the view that postural instability and sensory conflict are elements of motion sickness in anurans. Specifically, conflicts between tactile, vestibular and visual input seem essential for producing motion-induced emesis in anurans. Since the factors that induce motion sickness in R. schlegelii are the same ones that produce motion sickness in humans, arboreal frogs may be useful alternative models to mammals in motion sickness research.     

Participation of endogenous opioid peptides in the pathogenesis of motion sickness

Investigations were performed with 19 healthy male volunteers to specify a possible role of endogenous opioid peptides in the pathogenesis of motion sickness. For this purpose the test subjects were administered naloxone, a specific antagonist of opiates and opioids, before rotation and during rotation in a BU-4 armchair at a rate of 30 rpm. In addition, the content of beta-endorphin in blood plasma was measured. It was discovered that naloxone exerts both prophylactic and therapeutic effects as regards the simulated motion sickness. In this respect it was more efficacious than the reference drug scopolamine. After rotation there was a significant increase in the beta-endorphin content in the blood plasma of the test subjects. It is assumed that endogenous opioid peptides (in particular beta-endorphin) may be directly involved in the genesis of vestibulo-vegetative disorders in motion sickness.     

Brine shrimp development in space: ground-based data to shuttle flight results

The brine shrimp, Artemia salina, has been used as a model system to assess microgravity effects on developing organisms. Following fertilization and early development, the egg can arrest in early gastrula as a dehydrated cyst stage that is stable to harsh environments over long time periods. When salt water is added, the cysts can reactivate, with embryonic development and egg hatching occurring in about 24 h. A series of larval molts or instars, over about a 2 week period, results in the adult crustacean. We have assessed these developmental events in a closed syringe system, a bioprocessing module, in ground-based studies, and have conducted preliminary in-orbit experiments aboard the Space Shuttle Atlantis during the flights of STS-37 and STS-43. Although the in-flight data are limited, spectacular degrees of development have been achieved.