Cochlear Functional Changes and CGRP Modulation in a Chronic Nitroglycerin Migraine-Like Rat Model

Area of Science:

• Neuroscience
• Otolaryngology
• Pharmacology

Background:

• Auditory and vestibular symptoms are common in vestibular migraine, cochlear migraine, and Ménière's disease.
• The link between migraine pathophysiology and inner ear dysfunction is not fully understood.
• Calcitonin gene-related peptide (CGRP) is implicated in migraine but its role in cochlear dysfunction is unclear.

Purpose of the Study:

• To investigate if a migraine-like state impacts cochlear function in rats.
• To determine if CGRP is involved in these migraine-induced cochlear effects.

Main Methods:

• A repeated nitroglycerin (NTG) model was used in male Wistar rats.
• Rats received saline, NTG, or NTG plus the CGRP receptor antagonist olcegepant (OLC).
• Cochlear function was assessed using distortion-product otoacoustic emissions and auditory brain stem response; molecular markers were also analyzed.

Main Results:

• NTG induced frequency-dependent changes in auditory function and elevated TNF-α and trigeminal c-Fos.
• Olcegepant partially normalized these markers and attenuated NTG-associated cochlear functional changes.
• Differences in postsynaptic GluR2 puncta and regional CGRP changes were observed with olcegepant treatment.

Conclusions:

• Migraine-like trigeminovascular activation is mechanistically linked to early cochlear dysfunction.
• CGRP receptor blockade may offer therapeutic benefits for migraine patients experiencing cochlear or vestibular symptoms.
• Further research should explore sex-specific responses and hormonal influences.