The journal of headache and painOct 28, 2025

Disrupted cellular cleanup, brain nerve signals, and gut-brain communication in a new rat model of vestibular migraine: possible causes

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A nitroglycerin-plus-rotation rat model reproduced -like pain and balance features and linked them to , neural signaling, microbiome, and metabolomic changes.

Evidence

This animal-model study in male Sprague-Dawley rats combined behavioral testing, ELISA/WB/IF molecular assays, 16S rRNA gut profiling, untargeted serum LC-MS, and bioinformatics comparisons to VM patients and datasets.

Caveat

The model is experimental and male-rat based, and the gut-brain findings are associative mechanistic signals rather than validated therapeutic targets in patients.

Simplified

BACKGROUND: (VM) pathophysiology remains incompletely understood, partly due to lacking validated animal models replicating its dual vestibular-nociceptive phenotype. This study aimed to establish a VM-like rat model and investigate associated mechanisms and gut microbiota/Serum metabolomics alterations.

METHODS: Male Sprague‒Dawley (SD) rats were used to establish a VM-like rat model via cervical subcutaneous nitroglycerin injections combined with variable-speed rotational stimulation. Behavioral tests, including tests for mechanical and thermal thresholds, balance beam traversal, and motion sickness (MS) index, were conducted to assess vestibular and nociceptive phenotypes. Molecular analyses included ELISA/WB/IF for TRP channels, CGRP, NMDAR1-CaMKII-CREB pathway, and markers in blood or brain tissues (trigeminocervical complex (TCC), vestibular nuclei (VN), thalamus, and cerebellum). Gut microbiota (16 S rRNA sequencing) and serum metabolomics (untargeted LC-MS) were profiled. Bioinformatics utilized OMIM, GeneCards, and GSE157495 datasets.

RESULTS: VM-like rats presented significant mechanical/thermal hyperalgesia, prolonged balance beam traversal, and elevated MS index scores (p < 0.05). Molecular analyses revealed upregulated TRPA1/TRPV1/TRPM8 in blood, increased CGRP in TCC/VN (p < 0.05), activated NMDAR1-CaMKII-CREB pathway in VN, and impaired autophagic flux (↑LC3-II, ↑P62; p < 0.05) in both VM patients and VM-like rats. Gut microbiota showed reduced evenness, increased Lactobacillus, HT002, and Bifidobacterium; and decreased Lachnospiraceae_NK4A136_group, Lachnospiraceae_unclassified, and Ligilactobacillus. Serum metabolomics revealed decreased SMs/PCs/PEs, increased 2-ketobutyric acid/GABA, and enrichment in amino acid metabolism, sphingolipid signaling, and vitamin pathways.

CONCLUSIONS: This validated VM-like rat model recapitulates core clinical and molecular features of VM. Gut dysbiosis and serum metabolic perturbations provide novel insights into the gut-brain axis in VM pathogenesis, suggesting potential therapeutic targets.

Key numbers

↑

Increase in Levels

levels were significantly increased in and of rats.

3 of 10

Mechanical Hyperalgesia

rats exhibited significant mechanical hyperalgesia compared to group.

↑ index

Elevated Motion Sickness Index

rats showed significantly elevated index scores from day 3 onwards.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Disrupted cellular cleanup, brain nerve signals, and gut-brain communication in a new rat model of vestibular migraine: possible causes

Abstract

Key numbers

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief

Abstract

Key numbers

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the gut-brain axis brief