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

Kunkler PE, Ballard CJ, Pellman JJ, Zhang L, Oxford GS, Hurley JH - PLoS ONE (2014)

Bottom Line: Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia.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.

View Article: PubMed Central - PubMed

Affiliation: The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

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.

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Retrograde double labeling in the trigeminal ganglion.Representative images two weeks following retrograde labeling of the nasal epithelium (Fluorogold; blue) and middle cerebral artery (MCA) (DiI; red). Numerous labeled cells were observed throughout the trigeminal ganglion and frequently retrograde labeled cells from the nasal mucosa were observed near to or adjacent to those from the MCA. Scale bar 100 µm.
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pone-0103086-g005: Retrograde double labeling in the trigeminal ganglion.Representative images two weeks following retrograde labeling of the nasal epithelium (Fluorogold; blue) and middle cerebral artery (MCA) (DiI; red). Numerous labeled cells were observed throughout the trigeminal ganglion and frequently retrograde labeled cells from the nasal mucosa were observed near to or adjacent to those from the MCA. Scale bar 100 µm.

Mentions: Retrograde label from the nasal epithelium was most abundant in the dorsal half of the ipsilateral TG in V1 and V2 subdivisions consistent with previous reports [43], [44]. Small to medium sized labeled cells were distributed over the entire medial to lateral extent of the ipsilateral ganglion, though the highest density was localized along the dorsomedial border of the ganglion. As expected no labeled cell bodies were observed in the mandibular branch of the trigeminal nerve or in the contralateral ganglia. The pattern of retrograde labeling from the MCA and dura was similar to that observed from the nasal epithelium, but slightly more diffusely spread throughout the ganglion. Labeled neurons were prominent in the V1 and V2 subdivision of the ganglion, similar to previous reports [15], [29], though a small number of labeled neurons in the contralateral ganglia were also present. Co-localization of nasal and MCA/dural retrograde labels, an indicator of axonal collaterals supplying the distinct receptive fields, was not observed in any sections. In contrast, clusters of independently labeled neurons from each target were frequently observed to be clumped together (Fig. 5). Distance measurements between retrogradely labeled cells confirmed this observation (Table 1). The average nearest distance between individual Fluorogold (FG) nasal retrogradely labeled cells in the ganglia (n = 129) was 88.24±7.72 µm while that between retrogradely DiI labeled MCA cells (n = 110) was 120.90±12.05 µm. Distance measurements between FG labeled cells also revealed 37.2% of the cells (48 of 129 total labeled cells) were within 50 µm of the next closest FG labeled cell, and 70.5% of the total labeled population (91 of 129 cells) were within 100 µm. Slightly further distances were measured between nearest DiI labeled pairs, with 28.2% and 57.3% of the total population observed within 50 and 100 µm, respectively. The average nearest distance between a FG and DiI labeled cell was 95.01±8.98 µm, with distances similar to those for each separate population (24.8% and 69.8% of the total population observed within 50 and 100 um, respectively). The close proximity of these two afferent populations within the ganglia supports the potential involvement of chemical intraganglionic transmission to communicate signals from the nasal epithelium to the cranial blood vessels.


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

Kunkler PE, Ballard CJ, Pellman JJ, Zhang L, Oxford GS, Hurley JH - PLoS ONE (2014)

Retrograde double labeling in the trigeminal ganglion.Representative images two weeks following retrograde labeling of the nasal epithelium (Fluorogold; blue) and middle cerebral artery (MCA) (DiI; red). Numerous labeled cells were observed throughout the trigeminal ganglion and frequently retrograde labeled cells from the nasal mucosa were observed near to or adjacent to those from the MCA. Scale bar 100 µm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4117521&req=5

pone-0103086-g005: Retrograde double labeling in the trigeminal ganglion.Representative images two weeks following retrograde labeling of the nasal epithelium (Fluorogold; blue) and middle cerebral artery (MCA) (DiI; red). Numerous labeled cells were observed throughout the trigeminal ganglion and frequently retrograde labeled cells from the nasal mucosa were observed near to or adjacent to those from the MCA. Scale bar 100 µm.
Mentions: Retrograde label from the nasal epithelium was most abundant in the dorsal half of the ipsilateral TG in V1 and V2 subdivisions consistent with previous reports [43], [44]. Small to medium sized labeled cells were distributed over the entire medial to lateral extent of the ipsilateral ganglion, though the highest density was localized along the dorsomedial border of the ganglion. As expected no labeled cell bodies were observed in the mandibular branch of the trigeminal nerve or in the contralateral ganglia. The pattern of retrograde labeling from the MCA and dura was similar to that observed from the nasal epithelium, but slightly more diffusely spread throughout the ganglion. Labeled neurons were prominent in the V1 and V2 subdivision of the ganglion, similar to previous reports [15], [29], though a small number of labeled neurons in the contralateral ganglia were also present. Co-localization of nasal and MCA/dural retrograde labels, an indicator of axonal collaterals supplying the distinct receptive fields, was not observed in any sections. In contrast, clusters of independently labeled neurons from each target were frequently observed to be clumped together (Fig. 5). Distance measurements between retrogradely labeled cells confirmed this observation (Table 1). The average nearest distance between individual Fluorogold (FG) nasal retrogradely labeled cells in the ganglia (n = 129) was 88.24±7.72 µm while that between retrogradely DiI labeled MCA cells (n = 110) was 120.90±12.05 µm. Distance measurements between FG labeled cells also revealed 37.2% of the cells (48 of 129 total labeled cells) were within 50 µm of the next closest FG labeled cell, and 70.5% of the total labeled population (91 of 129 cells) were within 100 µm. Slightly further distances were measured between nearest DiI labeled pairs, with 28.2% and 57.3% of the total population observed within 50 and 100 µm, respectively. The average nearest distance between a FG and DiI labeled cell was 95.01±8.98 µm, with distances similar to those for each separate population (24.8% and 69.8% of the total population observed within 50 and 100 um, respectively). The close proximity of these two afferent populations within the ganglia supports the potential involvement of chemical intraganglionic transmission to communicate signals from the nasal epithelium to the cranial blood vessels.

Bottom Line: Accordingly resiniferatoxin also significantly reduces TRPV1 and CGRP immunostaining and TRPV1 and TRPA1 message levels in trigeminal ganglia.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.

View Article: PubMed Central - PubMed

Affiliation: The Department of Biochemistry and Molecular Biology, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.

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.

Show MeSH
Related in: MedlinePlus