Expression of Calcitonin Gene-Related Peptide in
Efferent Vestibular System and Vestibular Nucleus in
Rats with Motion Sickness
Wang Xiaocheng1, Shi Zhaohui2, Xue Junhui1, Zhang Lei1, Feng Lining1*, Zhang Zuoming1*
1Department of Clinical Aerospace Medicine, Key Laboratory of Aerospace Medicine of Ministry of Education, The Fourth Military Medical University, Xi’an, China,
2Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, China
Motion sickness presents a challenge due to its high incidence and unknown pathogenesis although it is a known fact that a
functioning vestibular system is essential for the perception of motion sickness. Recent studies show that the efferent
vestibular neurons contain calcitonin gene-related peptide (CGRP). It is a possibility that the CGRP immunoreactivity (CGRPi)
fibers of the efferent vestibular system modulate primary afferent input into the central nervous system; thus, making it
likely that CGRP plays a key role in motion sickness. To elucidate the relationship between motion sickness and CGRP, the
effects of CGRP on the vestibular efferent nucleus and the vestibular nucleus were investigated in rats with motion sickness.
Methods: An animal model of motion sickness was created by subjecting rats to rotary stimulation for 30 minutes via a
trapezoidal stimulation pattern. The number of CGRPi neurons in the vestibular efferent nucleus at the level of the facial
nerve genu and the expression level of CGRPi in the vestibular nucleus of rats were measured. Using the ABC method of
immunohistochemistry technique, measurements were taken before and after rotary stimulation. The effects of
anisodamine on the expression of CGRP in the vestibular efferent nucleus and the vestibular nucleus of rats with motion
sickness were also investigated.
Results and Discussion: Both the number of CGRPi neurons in the vestibular efferent nucleus and expression level in the
vestibular nucleus increased significantly in rats with motion sickness compared to that of controls. The increase of CGRP
expression in rats subjected to rotary stimulation 3 times was greater than those having only one-time stimulation.
Administration of anisodamine decreased the expression of CGRP within the vestibular efferent nucleus and the vestibular
nucleus in rats subjected to rotary stimulation. In conclusion, CGRP possibly plays a role in motion sickness and its
mechanism merits further investigation.
Citation: Xiaocheng W, Zhaohui S, Junhui X, Lei Z, Lining F, et al. (2012) Expression of Calcitonin Gene-Related Peptide in Efferent Vestibular System and
Vestibular Nucleus in Rats with Motion Sickness. PLoS ONE 7(10): e47308. doi:10.1371/journal.pone.0047308
Editor: Bruce Riley, Texas A&M University, United States of America
Received May 1, 2012; Accepted September 11, 2012; Published October 9, 2012
Copyright: ? 2012 Xiaocheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by grants from the Shaanxi Natural Science Fund 2009K17-02(46), China. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: firstname.lastname@example.org (FL); email@example.com (ZZ)
Motion sickness is a common and challenging problem. Various
physiological measurements for this problem have been tested.
However, no single parameter has yet been found to have a high
enough sensitivity and specificity for the diagnosis or prediction of
individual susceptibility to motion sickness. [1–3] Motion sickness
may be precipitated by conflicting sensory input – visual and
vestibular signals that do not match an internal model of expected
environmental stimuli. [1–4] It is well known that a functioning
vestibular system is essential for the perception of motion sickness.
 Theoretically, if sufficiently provocative motion stimulus is
introduced, anyone with a functioning vestibular system could be
susceptible.  However, thus far the underlying mechanism is
unclear. The innervations of the vestibular system include both the
afferent and efferent vestibular system (EVS). Vestibular sensory
organs in the inner ear are innervated by true efferent fibers
originating from brainstem neurons. Studies show that electrical
stimulation of EVS fibers can result in both facilitatory and
inhibitory modulation of the sensory activity in the afferent
vestibular system.  Therefore, EVS is considered to play a role
in the modulation of the afferent input from the peripheral
vestibular receptors to the central nervous system. 
Originally, efferent vestibular neurons (EVN) were assumed to
be cholinergic, but currently, more evidence demonstrates that the
efferent vestibular neurons contain both calcitonin gene-related
peptide (CGRP) and choline acetyltransferase (CHAT). CGRP is a
peptide with 37 amino acid residues translated from alternative
processing of mRNA transcribed from the calcitonin gene. [8–10]
CGRP is widely distributed in the central nervous system
including the vestibular pathways. CGRP can be detected in the
efferent pathways of the vestibular end-organs and the central
vestibular system. [7,11–13] Therefore, the role of CGRP in
modulating this afferent input into the central nervous system is of
fundamental importance in understanding neural processing in
general and in the etiology of motion sickness. However, at
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CGRP in Vestibular System of Rats with MS
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