EXCEED THE SPACE PROVIDED. Both the irritating as well asthe potentially debilitating _ymptoms of allergic airway disease are due in large parl to perturbation is neur6t_al activity. Thus sneezing, nonproductive coughing, increases mucus secretion, reversible bronchospasm, and inordinate sensations of dyspnea are a Consequence of abnormal afferent (sensory) input to the central nervous system, alterations in signal processing within the CNS, and/or alterations in the function of parasympathetic nerves. There has been much knowledge gained in the past two decades regarding the immunological and biochemical basis of the inflammation that accompanies allergic airway disease. Relatively little remains known, however, about how this inflammation modulates airway sensory and autonomic innervation such that the symptoms of disease occur. The long-range goal of this proposal is to develop at a better understanding of the mechanism and mediators involved in allergen-induced neuromodulation of the airways. The effect of allerlgen challenge on sensory afferent nerves and autonomic parasympathetic nerves innervating the airways will be investigated. Standard electrophysiologicat and immunohistochernical methods on airways isolated from guinea pigs and human tissue donors to directly address the mechanisms by which antigen challenge modulates neuronal function at a singel cell level in the airways. The results from this multidisciplinary approach should be of intrinsic value inproviding new knowledge regarding the cellular neurophysiology of the airways. The results may also shed new light on the complex pathophysiology of allergic airway diseases such as asthma, and ultimately suggest new therapeutic strategies for treatment of these complex diseases. PERFORMANCE SITE ========================================Section End===========================================
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