Reduction of Motion Sickness Through Targeting Histamine N-Methyltransferase in the Dorsal Vagal Complex of the Brain.

To investigate the role of histamine N-methyltransferase (HNMT) activity in the development of motion sickness (MS) in the dorsal vagal complex (DVC) to inform the development of new drugs for MS, Beagle dogs and Sprague-Dawley rats were rotated to simulate MS. HNMT expression in the brain stem and DVC was measured. The effects of systemic application of tacrine, an HNMT inhibitor, on the development of MS were observed. Moreover, we microinjected a histamine receptor H1 inhibitor, promethazine, into the DVC to verify the involvement of histaminergic neurotransmission in MS. Finally, lentiviral vectors were microinjected into the DVC to determine the effects of altered HNMT expression on MS. We found the following: 1) HNMT expression in the medulla oblongata of dogs and rats insusceptible to MS was higher than in susceptible animals; 2) tacrine dose-dependently promoted MS in both animals and raised histamine level in rat medulla oblongata; 3) blocking histaminergic neurotransmission in the DVC with promethazine inhibited MS; 4) rotatory stimulus induced an elevation in HNMT expression, and vestibular training elevated the basal level of HNMT in the DVC during habituation to MS; 5) in vivo transfection of a lentiviral vector packaged with the HNMT gene increased HNMT expression in the DVC and reduced MS; and 6) microinjection of a lentiviral vector driving the interference of HNMT gene expression in vivo significantly inhibited HNMT expression in the DVC and exacerbated MS. In conclusion, HNMT expression in the brain stem is inversely correlated with MS development. Increasing HNMT expression or stimulating its activity in the DVC could inhibit MS.

Predicting motion sickness during parabolic flight.

BACKGROUND: There are large individual differences in susceptibility to motion sickness. Attempts to predict who will become motion sick have had limited success. In the present study, we examined gender differences in resting levels of salivary amylase and total protein, cardiac interbeat intervals (R-R intervals), and a sympathovagal index and evaluated their potential to correctly classify individuals into two motion sickness severity groups. METHODS: Sixteen subjects (10 men and 6 women) flew four sets of 10 parabolas aboard NASA's KC-135 aircraft. Saliva samples for amylase and total protein were collected preflight on the day of the flight and motion sickness symptoms were recorded during each parabola. Cardiovascular parameters were collected in the supine position 1-5 days before the flight. RESULTS: There were no significant gender differences in sickness severity or any of the other variables mentioned above. Discriminant analysis using salivary amylase, R-R intervals and the sympathovagal index produced a significant Wilks' lambda coefficient of 0.36, p=0.006. The analysis correctly classified 87% of the subjects into the none-mild sickness or the moderate-severe sickness group. CONCLUSIONS: The linear combination of resting levels of salivary amylase, high-frequency R-R interval levels, and a sympathovagal index may be useful in predicting motion sickness severity.

[Image and quantity analysis of prostaglandin in rats' blood plasma and Na(+)-K(+)-ATPase in their cerebellum during the prevention of motion sickness by cinnarizine].

To study the mechanism of cinnarizine in preventing motion sickness, TXB2, 6-Keto-PGF1 alpha in rats' blood plasma and Na(+)-K(+)-ATPase activity in the endothelial cells of their cerebellar capillary were measured and analysed by a radioactive immunity analyser and a computer image system. The results showed that TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in the cinnarizine preventing group (CPG) decreased remarkably, compared with those in the motion sickness group(MSG) (p < 0.05). The activity of Na(+)-K(+)-ATPase in the endothelial cells of rats' cerebellar capillary in CPG was higher than that in MSG (p < 0.01). The authors suggest that the lower concentration of TXB2 and 6-Keto-PGF1 alpha in rats' blood plasma in CPG is closely related to cinnarizine which prevents Ca2+ from entering into the platelets and into the endothelial cells of blood vessels. The higher activity of Na(+)-K(+)-ATPase in the cerebellum may be caused by cinnarizene which dilates the blood vessels in the brain, increases the blood flow therein, and hinders Ca2+ from getting into the cerebellum cells. These change are believed to be the important mechanism of how cinnarizine prevents motion sickness.

Endocrine correlates of susceptibility to motion sickness.

Motion sickness releases ACTH, epinephrine, and norepinephrine. We are interested in endocrine responses to motion sickness, in adaptive responses leading to the resolution of the syndrome, and in how antimotion-sickness drugs influence the endocrine responses. Susceptible or insusceptible subjects were administered antimotion-sickness drugs prior to stressful stimulation. Insusceptible subjects displayed more pronounced elevations of ACTH, epinephrine, and norepinephrine after stressful motion. Predrug levels of ACTH were higher in insusceptible subjects (p less than 0.01). Acute blockade of hormone responses to stressful motion or alteration of levels of ACTH by drugs was not correlated with individual susceptibility. No correlation was apparent between epinephrine and ACTH release. These endocrine differences may represent neurochemical markers for susceptibility to motion, stress, or general adaptability, and it may be that the chronic modulation of their levels might be more effective in preventing motion sickness than the acute blockade or stimulation of specific receptors.