Back to the future:re-establishing guinea pig in vivo asthma models

Research using animal models of asthma is currently dominated by mouse models. This has been driven by the comprehensive knowledge on inflammatory and immune reactions in mice, as well as tools to produce genetically modified mice. Many of the identified therapeutic targets influencing airway hyper-responsiveness and inflammation in mouse models, have however been disappointing when tested clinically in asthma. It is therefore a great need for new animal models that more closely resemble human asthma. The guinea pig has for decades been used in asthma research and a comprehensive table of different protocols for asthma models is presented. The studies have primarily been focused on the pharmacological aspects of the disease, where the guinea pig undoubtedly is superior to mice. Further reasons are the anatomical and physiological similarities between human and guinea pig airways compared with that of the mouse, especially with respect to airway branching, neurophysiology, pulmonary circulation and smooth muscle distribution, as well as mast cell localization and mediator secretion. Lack of reagents and specific molecular tools to study inflammatory and immunological reactions in the guinea pig has however greatly diminished its use in asthma research. The aim in this position paper is to review and summarize what we know about different aspects of the use of guinea pig in vivo models for asthma research. The associated aim is to highlight the unmet needs that have to be addressed in the future

Reflex mechanisms in gastroesophageal reflux disease and asthma

This article presents a brief description of the reflex mechanisms responsible for cough and bronchospasm, and identifies several potential mechanisms by which gastroesophageal reflux (GER) may precipitate these reflexes. Airway and esophageal reflexes related to various mechanoreceptors and chemoreceptors have been elucidated, primarily in animal studies. Central nervous system (CNS) reflex pathways as well as local axon reflexes may each contribute to the pathogenesis of both asthma and GER disease (GERD). When activated, airway nociceptors precipitate defensive reflexes such as cough, bronchospasm, and mucus secretion. Nociceptors innervating both the airways and the esophagus respond to similar stimuli with defensive manuevers. The pathways of some esophageal and airway sensory nerves terminate in the same regions of the CNS. It appears possible that synergistic interactions between esophageal nociceptors and airway sensory nerves may precipitate the asthma-like symptoms associated with GERD. Copyright © 2003 Excerpta Medica Inc. All rights reserved

Autonomic neural control of the airways

The airways and lungs are innervated by both sympathetic and parasympathetic nerves. Cholinergic parasympathetic innervation is well conserved in the airways while the distribution of noncholinergic parasympathetic and adrenergic sympathetic nerves varies considerably amongst species. Autonomic nerve function is regulated primarily through reflexes initiated upon bronchopulmonary vagal afferent nerves. Central regulation of autonomic tone is poorly described but some key elements have been defined

Neuronal modulation of airway and vascular tone and their influence on nonspecific airways responsiveness in asthma

The autonomic nervous system provides both cholinergic and noncholinergic neural inputs to end organs within the airways, which includes the airway and vascular smooth muscle. Heightened responsiveness of the airways to bronchoconstrictive agents is a hallmark feature of reactive airways diseases. The mechanisms underpinning airways hyperreactivity still largely remain unresolved. In this paper we summarize the substantial body of evidence that implicates dysfunction of the autonomic nerves that innervate smooth muscle in the airways and associated vasculature as a prominent cause of airways hyperresponsiveness in asthma