Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Inner Ear Arginine Vasopressin-Vasopressin Receptor 2-Aquaporin 2 Signaling Pathway Is Involved in the Induction of Motion Sickness.

It has been identified that arginine vasopressin (AVP), vasopressin receptor 2(V2R), and the aquaporin 2 (AQP2) signaling pathway in the inner ear play important roles in hearing and balance functions through regulating the endolymph equilibrium; however, the contributions of this signaling pathway to the development of motion sickness are unclear. The present study was designed to investigate whether the activation of the AVP-V2R-AQP2 signaling pathway in the inner ear is involved in the induction of motion sickness and whether mozavaptan, a V2R antagonist, could reduce motion sickness. We found that both rotatory stimulus and intraperitoneal AVP injection induced conditioned taste aversion (a confirmed behavioral index for motion sickness) in rats and activated the AVP-V2R-AQP2 signaling pathway with a responsive V2R downregulation in the inner ears, and AVP perfusion in cultured epithelial cells from rat endolymphatic sacs induced similar changes in this pathway signaling. Vestibular training, V2R antagonist mozavaptan, or PKA inhibitor H89 blunted these changes in the V2R-AQP2 pathway signaling while reducing rotatory stimulus- or DDAVP (a V2R agonist)-induced motion sickness in rats and dogs. Therefore, our results suggest that activation of the inner ear AVP-V2R-AQP2 signaling pathway is potentially involved in the development of motion sickness; thus, mozavaptan targeting AVP V2Rs in the inner ear may provide us with a new application option to reduce motion sickness. SIGNIFICANCE STATEMENT: Motion sickness affects many people traveling or working. In the present study our results showed that activation of the inner ear arginine vasopressin-vaspopressin receptor 2 (V2R)-aquaporin 2 signaling pathway was potentially involved in the development of motion sickness and that blocking V2R with mozavaptan, a V2R antagonist, was much more effective in reducing motion sickness in both rat and dog; therefore, we demonstrated a new mechanism to underlie motion sickness and a new candidate drug to reduce motion sickness.

Profiling of cybersickness and balance disturbance induced by virtual ship motion immersion combined with galvanic vestibular stimulation.

Profile of cybersickness and balance disturbance induced by virtual ship motion alone and in combination with galvanic vestibular stimulation (GVS) remained unclear. Subjects were exposed to a ship deck vision scene under simulated Degree 5 or 3 sea condition using a head-mounted virtual reality display with or without GVS. Virtual ship motion at Degree 5 induced significant cybersickness with symptom profile: nausea syndrome > central (headache and dizziness) > peripheral (cold sweating) > increased salivation. During a single session of virtual ship motion exposure, GVS aggravated balance disturbance but did not affect most cybersickness symptoms except cold sweating. Repeated exposure induced cybersickness habituation which was delayed by GVS, while the temporal change of balance disturbance was unaffected. These results suggested that vestibular inputs play different roles in cybersickness and balance disturbance during virtual reality exposure. GVS might not serve as a potential countermeasure against cybersickness induced by virtual ship motion.

Sea Voyage Training and Motion Sickness Effects on Working Ability and Life Quality After Landing.

BACKGROUND: The effects of seasickness on working performance during motion exposure have been reported, while the aftereffects on working ability and life quality decline (WLD) still remain unclarified.METHODS: Two cohorts of healthy male Chinese subjects received either a single (SSV) or repeated (RSV) sea voyage training program on different vessels. A seasickness incidence (SSI) questionnaire was administered to assess the prevalence of seasickness symptoms (vomiting, nausea, other, or no symptoms). A WLD questionnaire was used to survey the general feeling of WLD (severe, moderate, slight, and none) by a 4-point score as well as the incidence rate (IR) of specific WLD items within 24 h after landing.RESULTS: The RSV cohort had lower overall IR of WLD than the SSV cohort (54.64% vs. 63.78%, N 657 for both cohorts). The landing ship trainees in both cohorts showed higher general WLD score and higher IRs of physical fatigue, sleep disorder, and spontaneous locomotion decrement than those trained on the small vessels. Subjects with vomiting or nausea had higher general WLD score and higher IRs of concentration distraction, physical fatigue, anorexia, and spontaneous locomotion decrement than those with no symptoms. Higher IRs of firing accuracy decline (SSV: 21.35% vs. 7.13%, 9.14%; RSV: 22.11% vs. 9.28%, 5.27%), equipment operation disturbance (SSV: 16.85% vs. 3.57%, 6.85%; RSV: 20.47% vs. 7.85%, 7.03%) were also observed in the vomiting subjects than those with other symptoms and no symptoms.DISCUSSION: Significant WLD after landing was associated with transportation types, seasickness severity, and habituation during sea voyage training.Qi R-R, Xiao S-F, Su Y, Mao Y-Q, Pan L-L, Li C-H, Lu Y-L, Wang J-Q, Cai Y-L. Sea voyage training and motion sickness effects on working ability and life quality after landing. Aerosp Med Hum Perform. 2021; 92(2):9298.