ReviewCentral mechanisms of airway sensation and cough hypersensitivity
Introduction
The airways are innervated by heterogeneous populations of jugular and nodose vagal ganglia sensory neurons that respond to a wide range of chemical and mechanical stimuli. Activation of these sensory neurons results in the transmission of information about the airway environment, firstly to the brainstem and then to higher order brain regions, allowing for the production of both respiratory and autonomic reflexes, as well as more complex behavioural respiratory responses. Collectively, these reflexes and respiratory behaviours serve to protect the airways from endogenous or exogenous stimuli that are potentially damaging and by doing so they contribute to the maintenance of adequate physiological respiratory function. The characterisation and physiology of airway vagal afferent neurons has been reviewed in detail, as has the neuroanatomical organisation of airway vagal afferent pathways in the brain [81], [9], [8], [15], [55], and as such the present review will only briefly cover these topics. Rather, we will focus on plasticity in the central neural circuitry involved in airway sensory processing and the current understanding of how this may provide insight into the airway sensory dysfunctions that underpin two prominent and related clinical presentations in pulmonary disease; excessive coughing and the urge-to-cough. In doing so, we will present some original data and draw from the advanced work that has been conducted in a comparable area of research (chronic pain), with the aim of highlighting important gaps in our current understanding of central cough neurophysiology.
Section snippets
Neuroanatomy of airway sensation
The central representation of jugular and nodose airway afferents has been investigated using a variety of physiological and neuroanatomical techniques [56], [57], [14], [58], [59]. Such studies have described in detail a primary termination site for airway vagal afferents in the brainstem nucleus of the solitary tract (nTS) and not surprisingly this nucleus has underpinned a substantial body of work on airway sensory neurotransmission [36], [41], [61], [66], [51], [1], [85]. However, our own
Can airway afferent circuits in the brain be altered in disease?
Neuronal sensitisation. Disordered airway sensory neural circuit activity, precipitated (for example) by the inflammatory processes induced by acute viral or allergen exposure or that associated with chronic illness in asthma or other respiratory diseases, contribute to excessive coughing and the increased perception of airway irritation common to many pulmonary disorders [12], [2], [31], [3], [82]. As such, it has become increasingly important to understand how airway sensory circuits are
Concluding remarks
Cough and the urge-to-cough contribute significantly to morbidity in pulmonary diseases and as such understanding the neuronal processes that underpin the development and maintenance of cough hypersensitivity is essential. We now have a reasonably advanced knowledge of the central processing circuits involved in airway sensation that will allow for hypothesis driven investigations of how the brain may contribute to chronic coughing in disease. Although this area of research is still in its
Funding
NHMRC of Australia. #1078943.
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