sensation,unmyelinated nerve fibers

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Airway nerves and dyspnea associated with inflammatory airway disease.

Undem Bradley J; Nassenstein (Profiled Author: UNDEM, BRADLEY)

Respiratory physiology & neurobiology 2009;167(1):36-44.

PubMedAbstract

The neurobiology of dyspnea is varied and complex, but there is little doubt

that vagal nerves within the airways are capable of causing or modulating some

dyspneic sensations, especially those associated with inflammatory airway

diseases. A major contributor to the dyspnea associated with inflammatory airway

disease is explained by airway narrowing and increases in the resistance to

airflow. The autonomic (parasympathetic) airway nerves directly contribute to

this by regulating bronchial smooth muscle tone and mucus secretion. In

addition, a component of the information reaching the brainstem via airway

mechanosensing and nociceptive afferent nerves likely contributes to the overall

sensations of breathing. The airway narrowing can lead to activation of low

threshold mechanosensitive stretch receptors, and vagal and spinal C-fibers as

well as some rapidly adapting stretch receptor in the airways that are directly

activated by various aspects of the inflammatory response. Inflammatory

mediators can induce long lasting changes in afferent nerve activity by

modulating the expression of key genes. The net effect of the increase in

afferent traffic to the brainstem modulates synaptic efficacy at the

second-order neurons via various mechanisms collectively referred to as central

sensitization. Many studies have shown that stimuli that activate

bronchopulmonary afferent nerves can lead to dyspnea in healthy subjects. A

logical extension of the basic research on inflammation and sensory nerve

function is that the role of vagal sensory nerve in causing or shaping dyspneic

sensations will be exaggerated in those suffering from inflammatory airway

disease.

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Mast cell-cholinergic nerve interaction in mouse airways.

Weigand Letitia A; Myers C; Meeker Sonya; Undem Bradley J (Profiled

Authors: MYERS, ALLEN; UNDEM, BRADLEY; MEEKER, SONYA)

Department of Medicine, s Hopkins University, Baltimore, MD, USA.

The Journal of physiology 2009;587(Pt 13):3355-62.

PubMedAbstract

We addressed the mechanism by which antigen contracts trachea isolated from

actively sensitized mice. Trachea were isolated from mice (C57BL/6J) that had

been actively sensitized to ovalbumin (OVA). OVA (10 microg ml(-1)) caused

histamine release (approximately total tissue content), and smooth muscle

contraction that was rapid in onset and short-lived (t(1/2) < 1 min), reaching

approximately 25% of the maximum tissue response. OVA contraction was mimicked

by 5-HT, and responses to both OVA and 5-HT were sensitive to 10

microm-ketanserin (5-HT(2) receptor antagonist) and strongly inhibited by

atropine (1microm). Epithelial denudation had no effect on the OVA-induced

contraction. Histological assessment revealed about five mast cells/tracheal

section the vast majority of which contained 5-HT. There were virtually no mast

cells in the mast cell-deficient (sash -/-) mouse trachea. OVA failed to elicit

histamine release or contractile responses in trachea isolated from sensitized

mast cell-deficient (sash -/-) mice. Intracellular recordings of the membrane

potential of parasympathetic neurons in mouse tracheal ganglia revealed a

ketanserin-sensitive 5-HT-induced depolarization and similar depolarization in

response to OVA challenge. These data support the hypothesis that

antigen-induced contraction of mouse trachea is epithelium-independent, and

requires mast cell-derived 5-HT to activate 5-HT(2) receptors on parasympathetic

cholinergic neurons. This leads to acetylcholine release from nerve terminals,

and airway smooth muscle contraction.

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Development, plasticity and modulation of visceral afferents.

Christianson A; Bielefeldt Klaus; Altier Christophe; Cenac Nicolas;

M; Gebhart Gerald F; High Karin W; Kollarik n; Randich Alan; Undem

Brad; Vergnolle Nathalie (Profiled Authors: KOLLARIK, MARIAN; UNDEM, BRADLEY)

University of Pittsburgh School of Medicine, Pittsburgh Center for Pain

Research, 200 Lothrop St., Pittsburgh, PA 16261, USA.

Brain research reviews 2009;60(1):171-86.

PubMedAbstract

Visceral pain is the most common reason for doctor visits in the US. Like

somatic pain, virtually all visceral pain sensations begin with the activation

of primary sensory neurons innervating the viscera and/or the blood vessels

associated with these structures. Visceral afferents also play a central role in

tissue homeostasis. Recent studies show that in addition to monitoring the state

of the viscera, they perform efferent functions through the release of small

molecules (e.g. peptides like CGRP) that can drive inflammation, thereby

contributing to the development of visceral pathologies (e.g. diabetes Razavi,

R., Chan, Y., Afifiyan, F.N., Liu, X.J., Wan, X., Yantha, J., Tsui, H., Tang,

L., Tsai, S., Santamaria, P., Driver, J.P., Serreze, D., Salter, M.W., Dosch,

H.M., 2006. TRPV1+ sensory neurons control beta cell stress and islet

inflammation in autoimmune diabetes, Cell 127 1123-1135). Visceral afferents are

heterogeneous with respect to their anatomy, neurochemistry and function. They

are also highly plastic in that their cellular environment continuously

influences their response properties. This plasticity makes them susceptible to

long-term changes that may contribute significantly to the development of

persistent pain states such as those associated with irritable bowel syndrome,

pancreatitis, and visceral cancers. This review examines recent insights into

visceral afferent anatomy and neurochemistry and how neonatal insults can affect

the function of these neurons in the adult. New approaches to the treatment of

visceral pain, which focus on primary afferents, will also be discussed.