Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries

doi:10.1016/j.neuroscience.2003.12.030

Neuroscience

Volume 124, Issue 4, 2004, Pages 919-927

https://doi.org/10.1016/j.neuroscience.2003.12.030 Get rights and content

Abstract

Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1—TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system.

Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles.

The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea.

Section snippets

Immunolocalization of TRPV1 and SP: animal preparation

Healthy male and female albino guinea-pigs (n=33; Hartley) with normal Preyer's reflex (300–350 g) were used in these studies. Albino guinea-pigs were chosen to avoid melanin pigments that may obscure the fluorescence signal. Animals were anesthetized with ketamine hydrochloride (100 mg/kg i.m.; Abbot Laboratories, North Chicago, IL, USA) and xylazine (2 mg/kg i.m.; Phoenix Scientific, Inc. St. Joseph, MO, USA). Anesthetized animals were perfused through the left heart ventricle with 200 ml

TRPV1 immunoreactivity

TRPV1 immunoreactivity was observed within axons in the adventitia of the BA and around the AICA, SMA, and radiating arterioles (Fig. 2A–D). The fibers were mostly longitudinal on the BA (Fig. 2A), but some branches ran circumferentially (e.g. arrow b in Fig. 2A) around the wall of AICA, SMA, and radiating arteriole (arrow b in Fig. 2A–D). TRPV1-expressing nerves were homogeneously labeled with no indication of varicosities. The diameters of the labeled fibers were largest around the BA and

Discussion

This study provides evidence for the innervation of the BA, AICA, and cochlear arteries by paravascular nerve fibers, which contain SP and exhibit TRPV1-immunoreactivity. Analysis of confocal images disclosed the colocalization of SP and TRPV1 immunoreactivities in paravascular nerve fibers. Circumstantial evidence indicates that SP- and TRPV1-immunoreactive fibers are of trigeminal origin. Previous studies by Suzuki et al. (1989) showed that SP- and CGRP-immunoreactive fibers around the BA

Acknowledgements

The present work was supported by NIH grants R01 DC00105, R01 DC03573, R01 DC04555, Fogarty International Research Collaboration Award R03 TW00502, R21 DC03955, OTKA T022363, T026025, T-032507 Hungary, and by the Soros Foundation, Hungary. We thank Dr. Michael Caterina for the gift of TRPV1 antibody. We would like to acknowledge Edward Porsov for technical assistance.

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Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries

Abstract

Section snippets

Immunolocalization of TRPV1 and SP: animal preparation

TRPV1 immunoreactivity

Discussion

Acknowledgements

Gen Pharmacol

Brain Res

Gen Pharmacol

Eur J Pharmacol

Neuroscience

Neuron

Hear Res

Neuroscience

Neuroscience

Neuroscience

Neural basis for regulation of cochlear blood flowPeptidergic and adrenergic innervation of the spiral modiolar artery of the guinea pig

Hear Res

The capsaicin receptorA heat-activated ion channel in the pain pathway

Nature

A capsaicin-receptor homologue with a high threshold for noxious heat

Nature

Mitochondrial calcium accumulation following activation of vanilloid (VR1) receptors by capsaicin in dorsal root ganglion neurons

Neuroscience

Capsaicin-sensitive neurogenic sensory vasodilatation in the dura mater of the rat

J Physiol

Effect of stimulation of trigeminal ganglion on regional cerebral blood flow in cats

Am J Physiol