Dai Mingjia, Kunin Mikhail, Raphan Theodore, Cohen Bernard
Department of Neurology, Mount Sinai School of Medicine, 1 East 100th Street, Box 1135, New York, NY 10029, USA.
Exp Brain Res. 2003 Jul;151(2):173-89. doi: 10.1007/s00221-003-1479-4. Epub 2003 May 29.
Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45 degrees over 2 s to and from the upright position while being rotated at 138 degrees /s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.
在以恒定速度旋转时，头部向一侧或从直立位向一侧侧倾（旋转时侧倾，RWR）会改变半规管相对于旋转轴的位置。这会产生垂直和水平眼震、定向障碍、眩晕和恶心。反复暴露后，受试者会产生适应性，在出现严重晕动病之前能够进行更多的头部运动。我们研究了异丙嗪是否能减轻眩晕或延迟适应性，眩晕的适应性是否与中枢前庭时间常数有关，即与速度存储的时间常数有关，以及晕动病的严重程度是否与眼速度轴偏离重力的程度有关。16名受试者在一项双盲交叉研究中接受了异丙嗪和安慰剂，该研究分两个连续的4天测试系列进行，间隔1个月，分别称为系列I和系列II。在用视频眼震图记录水平和垂直眼动时，受试者在围绕垂直轴以138度/秒旋转的同时，以大约45度的幅度在2秒内从直立位向一侧侧倾然后再回到直立位。晕动病程度从1（无不适）到终点20进行评分，达到20分时受试者会因过于不适而无法继续或即将呕吐。适应性由受试者在达到最大晕动病评分20分之前所做的头部运动次数来确定。在每次测试中，随着重复测试，头部运动次数稳步增加，异丙嗪组和安慰剂组的头部运动次数没有差异。每次测试中水平和垂直角前庭眼反射（aVOR）时间常数均下降，其下降与头部运动次数的增加密切相关。眩晕感的强度与眼速度轴偏离重力的程度有关；眼速度轴偏离重力越大，晕动病越严重。因此，异丙嗪既不能减轻与RWR相关的恶心，也不会延缓或加速适应性。aVOR时间常数与导致晕动病的头部运动次数之间的反比关系，以及晕动病严重程度与眼速度偏离重力的程度、强度和时间之间的关联，支持了这样一种假设，即速度存储的时空特性在前庭小脑的蚓小结和小舌与前庭核之间进行处理，可能是产生晕动病的冲突来源。
