# Orexin-A and motion sickness: a systematic review of animal model studies

**Authors:** Xu Cai, Long Zhao, Xin Wang, Jiahui Chen, Ying Yuan, Biao Gao, Yanli You

PMC · DOI: 10.3389/fphar.2025.1624080 · 2025-06-30

## TL;DR

This review explores how orexin-A, a brain chemical, may help reduce motion sickness in animals, but more high-quality research is needed to confirm its effectiveness.

## Contribution

The paper systematically reviews animal studies to evaluate orexin-A's role in motion sickness and highlights research gaps.

## Key findings

- Orexin-A reduced motion sickness symptoms in rat and cat models.
- Benefits may come from improved stomach motility and vestibular function.
- Study quality was limited by poor reporting and inconsistent methods.

## Abstract

Sensory input mismatches among the vestibular system, autonomic control, and visual perception cause motion sickness. Anticholinergics and antihistamines are commonly used but have limited efficacy and cause significant side effects. Orexin-A, a hypothalamic neuropeptide, has recently garnered attention for its potential role in controlling motion sickness.

To summarize current knowledge on the effects and mechanisms of orexin-A in reducing motion sickness, identify gaps, and propose future research directions.

Five qualified animal experiments were identified after searching PubMed, Scopus, Cochrane Library, Embase, and WoS. The SYRCLE tool was used to evaluate study quality, followed by a qualitative synthesis.

Orexin-A reduced motion-induced behavioral abnormalities, nausea, and vomiting in rat and cat models. These benefits are likely mediated by the modulation of hypothalamic nuclei activity, enhanced stomach motility, and improved vestibular function. However, several limitations were observed, including inadequate reporting on randomization, blinding, and allocation concealment, as well as heterogeneity in interventions and outcome measures.

Animal model studies indicates that orexin-A mitigates motion sickness (MS) symptoms in animal models, but overall certainty is low to moderate owing to risk of bias and indirectness. Rigorous, blinded studies with standardized outcomes—and ultimately, early-phase clinical trials, are needed to clarify therapeutic potential.

## Linked entities

- **Proteins:** Hcrt (hypocretin neuropeptide precursor)
- **Diseases:** motion sickness (MONDO:0008015)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Hcrt (hypocretin neuropeptide precursor) [NCBI Gene 25723] {aka orexin-A}
- **Diseases:** behavioral abnormalities (MESH:D001523), vomiting (MESH:D014839), MS (MESH:D009041), nausea (MESH:D009325)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Felis catus (cat, species) [taxon 9685]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12256435/full.md

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Source: https://tomesphere.com/paper/PMC12256435