Year of Publication

2008

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Medicine

Department

Physiology

First Advisor

Dr. Lu-Yuan Lee

Abstract

Airway hyperresponsivness (AHR) is one of most prominent pathophysiological features of asthma. Increasing evidence suggests that vagal bronchopulmonary afferents may be involved in the development of AHR. However, the underlying mechanisms are not clear. Therefore, the purpose of this dissertation was to investigate the effect of chronic airway inflammation induced by allergen sensitization on vagal bronchopulmonary afferents. The study was carried out in an animal model of allergic asthma. Brown-Norway rats were sensitized by intraperitoneal Ovalbumin (Ova) and exposed to aerosolized Ova 3 times/week for three weeks. Control rats received the vehicle. In vivo single-fiber recording technique was applied in this study. Our results showed that chronic Ova exposure caused an elevated baseline activity of pulmonary Cfibers, and a distinctly higher sensitivity of these afferents to chemical stimulants and lung inflation. After an acute Ova inhalation challenge, the increase in baseline activity and the excitability of pulmonary C-fibers were further augmented in sensitized rats, but not in control rats. In addition, sensitivity of pulmonary myelinated afferents to capsaicin was significantly elevated after chronic airway inflammation was induced by allergen. Furthermore, immunohistochemsitry data showed that, in nodose ganglia the proportion of transient receptor potential vanilloids type 1 channels (TRPV1)-expressing bronchopulmonary neurons was significantly higher in sensitized rats than in controls. This increase of TRPV1 expression was found mainly in neurofilament-positive neurons (myelinated neurons), but this effect was absent in jugular ganglia. In conclusion, allergen-induced airway inflammation caused a pronounced sensitizing effect on vagal pulmonary non-myelinated (C-fiber) afferents and elevated the sensitivity of vagal pulmonary myelinated afferents to capsaicin. The latter was accompanied by the upregulation of TRPV1 expression in these myelinated neurons.

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