title: Intraganglionic signaling as a novel nasal-meningeal pathway for TRPA1-dependent trigeminovascular activation by inhaled environmental irritants.
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.
authors: The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Phillip Edward
authors: PE
authors: Kunkler
authors: The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Carrie Jo
authors: CJ
authors: Ballard
authors: Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Jessica Joan
authors: JJ
authors: Pellman
authors: The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: LuJuan
authors: L
authors: Zhang
authors: Department of Pharmacology and Toxicology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Gerry Stephen
authors: GS
authors: Oxford
authors: The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors: Joyce Harts
authors: JH
authors: Hurley
mesh_terms: D000818:Animals; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure; D007509:Irritants / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008578:Meninges / Q000187:drug effects / Q000378:metabolism; D009296:Nasal Cavity / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000098:blood supply / Q000378:metabolism*
chemical_list: D004785:Environmental Pollutants; D007509:Irritants; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C480976:Trpa1 protein, rat