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Serotonin-induced plasma extravasation in the murine inner ear: possible mechanism of migraine-associated inner ear
1Department of Otolaryngology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Abstract:
Sensitivity to sound and vertigo are often components of migraine. Recent studies suggest that plasma extravasation from intradural blood vessels may contribute to migraine pain. This study documented plasma extravasation in the mouse inner ear after intravenous administration of serotonin (5-HT). Horseradish peroxidase (HRP) was injected intravenously to trace protein extravasation in mice, followed 15 min later by intravenous 5-HT or saline. Forty-five minutes later, mice were euthanized. HRP extravasation was visualized immunohistochemically and quantified densitometrically. Baseline and evoked extravasation in stria vascularis and tectorial membrane were indistinguishable from skin, dura mater and tympanic membrane. Brain parenchyma, Scarpa's ganglion, basal spiral ganglion and modiolus, and the central vestibular nerve segment showed no significant 5-HT-induced extravasation. In contrast, 5-HT produced extravasation in the apical spiral ganglion, modiolus, and intralabyrinthine superior and inferior vestibular nerve. Thus, inner ear plasma extravasation is a potential mechanism for migraine-associated vertigo and sound sensitivity.
Insights
Serotonin (5-HT) causes plasma leakage in the mouse inner ear, potentially explaining migraine symptoms like vertigo and sound sensitivity. This finding highlights a novel mechanism for migraine pathophysiology.
Area of Science:
- Neuroscience
- Otolaryngology
- Vascular Biology
Background:
- Migraine headaches are frequently accompanied by sound sensitivity (hyperacusis) and vertigo.
- Intradural plasma extravasation from blood vessels is a proposed mechanism contributing to migraine pain.
- The role of inner ear vascular permeability in migraine pathophysiology remains largely unexplored.
Purpose of the Study:
- To investigate whether serotonin (5-HT), a key mediator in migraine, induces plasma extravasation within the mouse inner ear.
- To determine if inner ear plasma leakage is associated with migraine-related symptoms such as vertigo and sound sensitivity.
Main Methods:
- Intravenous injection of a tracer, horseradish peroxidase (HRP), in mice to visualize protein extravasation.
- Administration of intravenous serotonin (5-HT) or saline to induce or control for plasma extravasation.
- Immunohistochemical visualization and densitometric quantification of HRP extravasation in various inner ear structures and control tissues.
Main Results:
- Serotonin (5-HT) induced significant plasma extravasation in specific regions of the inner ear, including the apical spiral ganglion, modiolus, and intralabyrinthine vestibular nerves.
- No significant 5-HT-induced extravasation was observed in the stria vascularis, tectorial membrane, skin, dura mater, tympanic membrane, brain parenchyma, Scarpa's ganglion, basal spiral ganglion, or central vestibular nerve.
- The pattern of extravasation suggests a targeted effect of 5-HT on certain inner ear vascular beds.
Conclusions:
- Plasma extravasation within the inner ear, specifically in the vestibular nerve pathways and spiral ganglion, is a potential mechanism underlying migraine-associated vertigo and sound sensitivity.
- These findings implicate inner ear vascular changes as a critical component of migraine pathophysiology.
- Targeting inner ear vascular permeability could offer new therapeutic strategies for managing migraine symptoms.
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