Pulmonary nociceptors are potentially connected with neuroepithelial bodies.
ABSTRACT Airway sensory receptors regulate cardiopulmonary function by providing constant information about the mechanical and chemical status of the lung to the central nervous system (CNS). There are at least three airway sensor types: slowly adapting receptors (SARs), rapidly adapting receptors (RARs), and C-fiber receptors (CFRs). We recently identified additional A-delta fiber receptors in intact rabbits that are different from SARs and RARs. Having a high mechanical threshold, they respond to hypertonic saline and are termed high threshold A-delta receptors (HTARs). SARs and RARs monitor airway mechanical changes, whereas HTARs and CFRs sense chemical alterations and may serve as nociceptors. As with nociceptors in other tissue, the latter are activated during lung inflammatory processes. Also, the airway houses neuroendocrine cells aggregated in organoids called neuroepithelial bodies (NEBs). NEBs are richly innervated by nerve fibers from different origins. Similar in structure to the carotid bodies, NEBs are believed to be sensors, with at least some sensory fibers that have cell bodies in the nodose ganglia. Therefore, they may serve CNS reflex functions. Strategically located at airway bifurcations, NEBs may signal the chemical composition of or presence of irritants in the air. This study intends to explore the possibility that NEBs are associated with nociceptors.
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ABSTRACT: The effect of serotonin on capsaicin-sensitive vagal C-fiber afferent nerves was evaluated in an ex-vivo vagally innervated mouse lung preparation. Action potentials arising from receptive fields in the lungs were recorded with an extracellular electrode positioned in the nodose/jugular ganglion. Among the 62 capsaicin-sensitive C-fibers studied (conduction velocity ~0.5 m/s), 71% were of the nodose phenotype and 29% of the jugular phenotype. The nodose C-fibers responded strongly to serotonin and this effect was blocked with the 5-HT3-receptor antagonist ondansetron. Using single cell rt-PCR, we noted that the vast majority of nodose neurons retrogradely labeled from the lung, expressed 5-HT3 receptor mRNA. The jugular C-fibers also responded strongly to serotonin with action potential discharge, but this effect was not inhibited by ondansetron. Lung-specific jugular neurons did not express 5-HT3 receptor mRNA but frequently expressed 5-HT1 or 5-HT4 receptor mRNA. Mast cells are the major source of serotonin in healthy murine airways. Ovalbumin-induced mast cell activation in actively sensitized lungs caused action potential discharge in jugular but not nodose C-fibers. The data show that vagal C-fibers in the respiratory tract of the mouse are strongly activated by serotonin. Depending on the C-fiber subtype both 5-HT3 and non-5-HT3 mechanisms are involved.The Journal of Physiology 08/2012; · 4.38 Impact Factor
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ABSTRACT: Neuroepithelial bodies (NEBs) serve a niche for lung stem cells and proliferate in a variety of pulmonary diseases. We hypothesize that NEBs play an important role in lung injury repair processes, such as during pulmonary fibrosis. To test this hypothesis, we examined NEBs in a bleomycin-induced lung fibrosis mouse model. We divided FVB/NJ mice into bleomycin-treated (BL) and normal saline-treated (NS) groups. Two weeks after intravenous treatment we immune-stained NEBs with anti-calcitonin gene-related peptide (CGRP) in whole mount preparations and found that the number of NEBs per unit area of airway almost tripled in the BL group (1.11±0.28 number/mm(2); n=5) compared with the NS group (0.32±0.14 number/mm(2); n=4, P=0.001). The size of NEBs increased significantly in the BL group. Our findings support that NEBs play an important role in the pathogenesis of pulmonary fibrosis.Respiratory Physiology & Neurobiology 01/2014; · 1.97 Impact Factor
Article: Sensory nerves in lung and airways.[Show abstract] [Hide abstract]
ABSTRACT: Sensory nerves innervating the lung and airways play an important role in regulating various cardiopulmonary functions and maintaining homeostasis under both healthy and disease conditions. Their activities conducted by both vagal and sympathetic afferents are also responsible for eliciting important defense reflexes that protect the lung and body from potential health-hazardous effects of airborne particulates and chemical irritants. This article reviews the morphology, transduction properties, reflex functions, and respiratory sensations of these receptors, focusing primarily on recent findings derived from using new technologies such as neural immunochemistry, isolated airway-nerve preparation, cultured airway neurons, patch-clamp electrophysiology, transgenic mice, and other cellular and molecular approaches. Studies of the signal transduction of mechanosensitive afferents have revealed a new concept of sensory unit and cellular mechanism of activation, and identified additional types of sensory receptors in the lung. Chemosensitive properties of these lung afferents are further characterized by the expression of specific ligand-gated ion channels on nerve terminals, ganglion origin, and responses to the action of various inflammatory cells, mediators, and cytokines during acute and chronic airway inflammation and injuries. Increasing interest and extensive investigations have been focused on uncovering the mechanisms underlying hypersensitivity of these airway afferents, and their role in the manifestation of various symptoms under pathophysiological conditions. Several important and challenging questions regarding these sensory nerves are discussed. Searching for these answers will be a critical step in developing the translational research and effective treatments of airway diseases. Published 2014. Compr Physiol 4:287-324, 2014.Comprehensive Physiology. 01/2014; 4(1):287-324.