Mechanisms underlying the neuronal-based symptoms of allergy

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 6; pp. 1521 - 1534
• Main Authors: Undem, Bradley J., Taylor-Clark, Thomas
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2014; Elsevier; Elsevier Limited
• Subjects: action potential; afferent; Afferent Pathways; airways; allergen; Allergens - immunology; Allergies; Allergy; Allergy and Immunology; Animals; anti-inflammatory; autonomic; Autonomic Pathways; Biological and medical sciences; bronchospasm; C-fiber; Central Nervous System; cough; critical periods; cytokine; degranulation; depolarization; dorsal root; dysfunction; Dysphagia; efferent; enteric; Enteric Nervous System; eye; Fundamental and applied biological sciences. Psychology; Fundamental immunology; ganglia; Ganglia, Sensory; gut; histamine; Humans; hypersecretion; Hypersensitivity - diagnosis; Hypersensitivity - etiology; IgE; Immune system; Immunopathology; inflammation; innervation; ion channel; irritant; itch; jugular; leukotriene; Lipids; lungs; mast cell; mast cell mediators; mast cell-nerve interactions; Medical sciences; Motility; myenteric; nerve; Nervous system; Neuroimmunomodulation; Neurons; Neurons - metabolism; nociceptor; nodose; nucleus tractus solitarious; pain; parasympathetic; Phenotype; phenotypic switch; plasticity; Pneumology; prostaglandin; receptor; reflex; Respiratory system : syndromes and miscellaneous diseases; Rodents; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sensory; skin; Spinal cord; steroids; sympathetic; symptoms; transient receptor potential channels; trigeminal; vagal; PGD2; Allergy; allergen; nociceptor; transient receptor potential channels; TRK; cough; TRP; lungs; trigeminal; innervation; cytokine; prostaglandin; plasticity; NGF; mast cell-nerve interactions; eye; symptoms; nerve; C-fiber; efferent; afferent; CGRP; autonomic; histamine; sympathetic; IgE; leukotriene; gut; skin; airways; CNS; GFL; dysfunction; ion channel; inflammation; anti-inflammatory; jugular; nodose; phenotypic switch; itch; pain; bronchospasm; TRPA1; dorsal root; mast cell; myenteric; reflex; vagal; TRPV1; action potential; enteric; receptor; parasympathetic; GDNF; sensory; hypersecretion; mast cell mediators; depolarization; ganglia; critical periods; motility; steroids; degranulation; irritant; nucleus tractus solitarious; Calcitonin gene–related peptide; Transient receptor potential vanilloid 1; Central nervous system; Nerve growth factor; Glial-derived neurotrophic factor family ligand; Tyrosine kinase receptor; Transient receptor potential ankyrin 1; Prostaglandin D 2; Glial-derived growth factor; Transient receptor potential; PGD 2; Skin disease; Lung; Ionic channel; Respiratory system; Bronchospasm; Eye; Visual system; Electrodiagnosis; Autonomic nervous system; Etiology; Eicosanoid; Bronchus disease; Digestive system; Arachidonic acid derivatives; Gut; Dysfunction; Mast cell; Skin; Nucleus; Spinal cord; Fiber; Electrophysiology; Action potential; Pruritus; Mechanism; Depolarization; Respiratory tract; Nociceptor; Pain; Trigeminal nerve; Reflex; Respiratory disease; Inflammation; Sympathetic nervous system; Hypersecretion; Cough; Symptomatology; Neuron; Degranulation; Parasympathetic nervous system; Allergen
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2013.11.027

Persons with allergies present with symptoms that often are the result of alterations in the nervous system. Neuronally based symptoms depend on the organ in which the allergic reaction occurs but can include red itchy eyes, sneezing, nasal congestion, rhinorrhea, coughing, bronchoconstriction, airway mucus secretion, dysphagia, altered gastrointestinal motility, and itchy swollen skin. These symptoms occur because mediators released during an allergic reaction can interact with sensory nerves, change processing in the central nervous system, and alter transmission in sympathetic, parasympathetic, and enteric autonomic nerves. In addition, evidence supports the idea that in some subjects this neuromodulation is, for reasons poorly understood, upregulated such that the same degree of nerve stimulus causes a larger effect than seen in healthy subjects. There are distinctions in the mechanisms and nerve types involved in allergen-induced neuromodulation among different organ systems, but general principles have emerged. The products of activated mast cells, other inflammatory cells, and resident cells can overtly stimulate nerve endings, cause long-lasting changes in neuronal excitability, increase synaptic efficacy, and also change gene expression in nerves, resulting in phenotypically altered neurons. A better understanding of these processes might lead to novel therapeutic strategies aimed at limiting the suffering of those with allergies.