Serotonin-induced plasma extravasation in the murine inner ear: possible mechanism of migraine-associated inner ear

J-W Koo1, C D Balaban

  • 1Department of Otolaryngology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.

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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