Distribution of intranasal lidocaine and its effect on electrically-evoked calcium signals in mouse trigeminal ganglion neurons

Background - Lidocaine applied intranasally has shown promise in treating post-dural puncture headache and has been explored as a potential treatment for cluster headache and migraine. However, the mechanisms underlying its analgesic effects remain unclear. This study aimed to determine the concentr...

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Autores principales: Tiebl, Lisa (Autor) , Solinski, Hans Jürgen (Autor) , Belejova, Sara (Autor) , Soares, Sabrina (Autor) , Pitzer, Claudia (Autor) , Palkovacs, Roland (Autor) , Poschet, Gernot (Autor) , Schmelz, Martin (Autor) , Oehler, Beatrice (Autor) , Carr, Richard (Autor)
Formato: Article (Journal)
Lenguaje:inglés
Publicado: Jun 2026
In: Cephalalgia
Year: 2026, Volumen: 46, Número: 6, Pages: 1-15
ISSN:1468-2982
DOI:10.1177/03331024261453548
Acceso en línea:Verlag, kostenfrei, Volltext: https://doi.org/10.1177/03331024261453548
Verlag, kostenfrei, Volltext: https://journals.sagepub.com/doi/10.1177/03331024261453548
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Notas de Autor:Lisa Tiebl, Hans Jürgen Solinski, Sara Belejova, Sabrina Soares, Claudia Pitzer, Roland Palkovacs, Gernot Poschet, Martin Schmelz, Beatrice Oehler, and Richard Carr
Descripción
Sumario:Background - Lidocaine applied intranasally has shown promise in treating post-dural puncture headache and has been explored as a potential treatment for cluster headache and migraine. However, the mechanisms underlying its analgesic effects remain unclear. This study aimed to determine the concentration of lidocaine that reaches target tissues after intranasal application and its impact on the excitability of trigeminal ganglion neurons. - Methods - A mouse model was used to examine lidocaine (10%) distribution after intranasal administration, employing liquid chromatography-mass spectrometry (LC-MS). Fluorescence calcium imaging with electrical field stimulation on acutely cultured murine trigeminal ganglion cells was applied to determine the effects of the pre-determined lidocaine concentrations on their excitability. - Results - After intranasal application, lidocaine concentrations ranged from approximately 2.5 μM in plasma to 7 μM in trigeminal ganglia. Calcium imaging revealed that 100 μM lidocaine was required to decrease electrical responses in capsaicin-unresponsive trigeminal ganglion neurons. In capsaicin-responsive nociceptive neurons such an inhibition was already observed at 10 μM lidocaine and these neurons also displayed a sustained increase in calcium that failed to return to baseline levels. - Conclusions - These findings suggest that intracranial lidocaine concentrations after intranasal administration are sufficiently high to selectively affect depolarized trigeminal nociceptors with ongoing activity, providing a potential mechanism for the analgesic effects of intranasally applied lidocaine. These results have implications for the use of intranasal lidocaine as a treatment for headache.
Notas:Online veröffentlicht: 24. Juni 2026
Gesehen am 31.07.2026
Descripción Física:Online Resource
ISSN:1468-2982
DOI:10.1177/03331024261453548