Sensory receptors in the visceral pleura: neurochemical coding and live staining in whole mounts.

Today, diagnosis and treatment of chest pain related to pathologic changes in the visceral pleura are often difficult. Data in the literature on the sensory innervation of the visceral pleura are sparse. The present study aimed at identifying sensory end-organs in the visceral pleura, and at obtaining more information about neurochemical coding. The immunocytochemcial data are mainly based on whole mounts of the visceral pleura of control and vagally denervated rats. It was shown that innervation of the rat visceral pleura is characterized by nerve bundles that enter in the hilus region and gradually split into slender bundles with a few nerve fibers. Separate nerve fibers regularly give rise to characteristic laminar terminals. Because of their unique association with the elastic fibers of the visceral pleura, we decided to refer to them as "visceral pleura receptors" (VPRs). Cryostat sections of rat lungs confirmed a predominant location on mediastinal and interlobar lung surfaces. VPRs can specifically be visualized by protein gene product 9.5 immunostaining, and were shown to express vesicular glutamate transporters, calbindin D28K, Na+/K+-ATPase, and P2X3 ATP-receptors. The sensory nerve fibers giving rise to VPRs appeared to be myelinated and to have a spinal origin. Because several of the investigated proteins have been reported as markers for sensory terminals in other organs, the present study revealed that VPRs display the neurochemical characteristics of mechanosensory and/or nociceptive terminals. The development of a live staining method, using AM1-43, showed that VPRs can be visualized in living tissue, offering an interesting model for future physiologic studies.

[1]  J. Kessler,et al.  Vesicular glutamate transporters type 1 and 2 expression in axon terminals of the rat nucleus of the solitary tract , 2006, Neuroscience.

[2]  D. Adriaensen,et al.  Sensory receptors in the airways: neurochemical coding of smooth muscle-associated airway receptors and pulmonary neuroepithelial body innervation , 2006, Autonomic Neuroscience.

[3]  D. Weinreich,et al.  Reflex regulation of airway sympathetic nerves in guinea‐pigs , 2006, The Journal of physiology.

[4]  Y. Jammes,et al.  Respiratory and circulatory effects of parietal pleural afferent stimulation in rabbits. , 2006, Journal of applied physiology.

[5]  D. Gozal,et al.  Bradykinin B2 receptors mediate pulmonary sympathetic afferents induced reflexes in rabbits. , 2006, Life sciences.

[6]  D. Adriaensen,et al.  Neurochemical characterisation of sensory receptors in airway smooth muscle: comparison with pulmonary neuroepithelial bodies , 2006, Histochemistry and Cell Biology.

[7]  Y. Jammes,et al.  Identification and properties of parietal pleural afferents in rabbits , 2005, The Journal of physiology.

[8]  S. Mazzone.  An overview of the sensory receptors regulating cough , 2005, Cough.

[9]  D. Adriaensen,et al.  Selective visualisation of neuroepithelial bodies in vibratome slices of living lung by 4-Di-2-ASP in various animal species , 2005, Cell and Tissue Research.

[10]  R. W. Banks,et al.  Autogenic modulation of mechanoreceptor excitability by glutamate release from synaptic‐like vesicles: evidence from the rat muscle spindle primary sensory ending , 2005, The Journal of physiology.

[11]  S. Mazzone.  Sensory regulation of the cough reflex. , 2004, Pulmonary pharmacology & therapeutics.

[12]  E. Mugnaini,et al.  Merkel cells, corpuscular nerve endings and free nerve endings in the mouse palatine mucosa express three subtypes of vesicular glutamate transporters , 2004, Journal of neurocytology.

[13]  Jun Fukuda,et al.  Identification of live hair cells in rat cochlear sections in culture with FM1-43 fluorescent dye , 2004, Neuroscience Letters.

[14]  W. Kummer,et al.  Catecholamines and catecholamine-synthesizing enzymes in guinea-pig sensory ganglia , 1990, Cell and Tissue Research.

[15]  G. Burnstock,et al.  Quantification of neuroepithelial bodies and their innervation in fawn-hooded and Wistar rat lungs. , 2004, American journal of respiratory cell and molecular biology.

[16]  W. Neuhuber,et al.  Intraganglionic laminar endings in the rat esophagus contain purinergic P2X2 and P2X3 receptor immunoreactivity , 2003, Anatomy and Embryology.

[17]  A. Reissig,et al.  Transthoracic Ultrasound of Lung and Pleura in the Diagnosis of Pulmonary Embolism: A Novel Non-Invasive Bedside Approach , 2003, Respiration.

[18]  J. T. Corwin,et al.  Lighting up the Senses: FM1-43 Loading of Sensory Cells through Nonselective Ion Channels , 2003, The Journal of Neuroscience.

[19]  W. Neuhuber,et al.  Vesicular glutamate transporter 2 immunoreactivity in putative vagal mechanosensor terminals of mouse and rat esophagus: indication of a local effector function? , 2003, Cell and Tissue Research.

[20]  G. Burnstock,et al.  Dual sensory innervation of pulmonary neuroepithelial bodies. , 2003, American journal of respiratory cell and molecular biology.

[21]  M. Dobretsov,et al.  Stretch receptor-associated expression of α3 isoform of the na+,k+-atpase in rat peripheral nervous system , 2003, Neuroscience.

[22]  J. Fukuda,et al.  Long-term staining of live Merkel cells with FM dyes , 2003, Cell and Tissue Research.

[23]  J. Fukuda,et al.  Staining of Living Merkel Cells with FM Dyes , 2003 .

[24]  D. Adriaensen,et al.  Vesicular glutamate transporter 2 is expressed in different nerve fibre populations that selectively contact pulmonary neuroepithelial bodies , 2003, Histochemistry and Cell Biology.

[25]  Jean-Pierre Timmermans,et al.  Triple Immunofluorescence Staining with Antibodies Raised in the Same Species to Study the Complex Innervation Pattern of Intrapulmonary Chemoreceptors , 2002, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[26]  Evidence for activity-dependent modulation of sensory-terminal excitability in spindles by glutamate release from synaptic-like vesicles. , 2002, Advances in experimental medicine and biology.

[27]  J.S.P. Jones.  The Pleura in Health and Disease , 2001, Lung.

[28]  L. Palmer,et al.  Chest pain in asbestos-exposed individuals with benign pleural and parenchymal disease. , 2000, American journal of respiratory and critical care medicine.

[29]  G. Burnstock,et al.  Intraepithelial vagal sensory nerve terminals in rat pulmonary neuroepithelial bodies express P2X(3) receptors. , 2000, American journal of respiratory cell and molecular biology.

[30]  W. Betz,et al.  Monitoring secretory membrane with FM1-43 fluorescence. , 1999, Annual review of neuroscience.

[31]  H. Berthoud,et al.  Vagal and spinal afferent innervation of the rat esophagus: A combined retrograde tracing and immunocytochemical study with special emphasis on calcium‐binding proteins , 1998, The Journal of comparative neurology.

[32]  C. Wedekind.  Receptive properties of primary afferent fibres from rabbit pleura, in vitro. , 1997, Somatosensory & motor research.

[33]  J. Lübke,et al.  FM1-43 dye ultrastructural localization in and release from frog motor nerve terminals. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. Lawrence.  Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: NEUROTRANSMITTER MECHANISMS OF RAT VAGAL AFFERENT NEURONS , 1995, Clinical and experimental pharmacology & physiology.

[35]  B. Droz,et al.  Innervation of Putative Rapidly Adapting Mechanoreceptors by Calbindin‐ and Calretinin‐immunoreactive Primary Sensory Neurons in the Rat , 1994, The European journal of neuroscience.

[36]  V. Rusch.  Diagnosis and treatment of pleural mesothelioma. , 1990, Seminars in surgical oncology.

[37]  L. Hochholzer,et al.  Localized Benign and Malignant Fibrous Tumors of the Pleura: A Clinicopathologic Review of 223 Cases , 1989, The American journal of surgical pathology.

[38]  Donat We,et al.  Chest Pain: Cardiac and Non-Cardiac Causes , 2011 .

[39]  I. Black,et al.  Catecholaminergic primary sensory neurons: autonomic targets and mechanisms of transmitter regulation. , 1987, Federation proceedings.

[40]  M. Costa,et al.  Light and electron microscopic immunocytochemistry of the same nerves from whole mount preparations. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[41]  M. Hodson,et al.  Malignant mesothelioma of the pleura: clinical aspects and symptomatic treatment. , 1984, European journal of respiratory diseases.

[42]  B. McNeil,et al.  Analysis of the differential diagnosis and assessment of pleuritic chest pain in young adults. , 1983, The American journal of medicine.

[43]  I. Black,et al.  Expression of catecholaminergic characteristics by primary sensory neurons in the normal adult rat in vivo. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[44]  G. Rosen,et al.  Chemical pleuritis as the cause of acute chest pain following high‐dose methotrexate treatment , 1983, Cancer.

[45]  J M Krauhs,et al.  Structure of rat aortic baroreceptors and their relationship to connective tissue , 1979, Journal of neurocytology.

[46]  F. L. Dwinnell.  Studies on the nerve endings in the visceral pleura. , 1966, The American journal of anatomy.

[47]  A. Mclaughlin.  Nerves and nerve endings in the visceral pleura of the cat , 1933, The Journal of physiology.

[48]  O. Larsell.  The ganglia, plexuses, and nerve‐terminations of the mammalian lung and pleura pulmonalis , 1922 .

[49]  O. Larsell.  Nerve terminations in the lung of the rabbit , 1921 .

[50]  J. A. Capps.  AN EXPERIMENTAL STUDY OF THE PAIN SENSE IN THE PLEURAL MEMBRANES , 1911 .