Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants

Phillip Edward Kunkler, Carrie Jo Ballard, Jessica Joan Pellman, LuJuan Zhang, Gerry Stephen Oxford, Joyce Hurley

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Headache is the most common symptom associated with air pollution, but little is understood about the underlying mechanism. Nasal administration of environmental irritants activates the trigeminovascular system by a TRPA1-dependent process. This report addresses questions about the anatomical pathway involved and the function of TRP channels in this pathway. TRPV1 and TRPA1 are frequently co-localized and interact to modulate function in sensory neurons. We demonstrate here that resiniferatoxin ablation of TRPV1 expressing neurons significantly reduces meningeal blood flow responses to nasal administration of both TRPV1 and TRPA1 agonists. Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia. Sensory neurons of the trigeminal ganglia innervate the nasal epithelium and the meninges, but the mechanism and anatomical route by which nasal administration evokes meningeal vasodilatation is unclear. Double retrograde labeling from the nose and meninges reveals no co-localization of fluorescent label, however nasal and meningeal labeled cells are located in close proximity to each other within the trigeminal ganglion. Our data demonstrate that TRPV1 expressing neurons are important for TRPA1 responses in the nasal-meningeal pathway. Our data also suggest that the nasal-meningeal pathway is not primarily by axon reflex, but may instead result from intraganglionic transmission.

Original languageEnglish
Article numbere103086
JournalPLoS One
Volume9
Issue number7
DOIs
StatePublished - Jul 31 2014

Fingerprint

Irritants
Nose
Intranasal Administration
Trigeminal Ganglion
Neurons
intranasal administration
Chemical activation
Meninges
meninges
Sensory Receptor Cells
sensory neurons
neurons
Nasal Mucosa
Air Pollution
Ablation
Air pollution
headache
Vasodilation
vasodilation
Labeling

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants. / Kunkler, Phillip Edward; Ballard, Carrie Jo; Pellman, Jessica Joan; Zhang, LuJuan; Oxford, Gerry Stephen; Hurley, Joyce.

In: PLoS One, Vol. 9, No. 7, e103086, 31.07.2014.

Research output: Contribution to journalArticle

Kunkler, Phillip Edward ; Ballard, Carrie Jo ; Pellman, Jessica Joan ; Zhang, LuJuan ; Oxford, Gerry Stephen ; Hurley, Joyce. / Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants. In: PLoS One. 2014 ; Vol. 9, No. 7.
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