Sensory Nerves and Airway Irritability

Abstract

The lung, like many other organs, is innervated by a variety of sensory nerves and by nerves of the parasympathetic and sympathetic nervous systems that regulate the function of cells within the respiratory tract. Activation of sensory nerves by both mechanical and chemical stimuli elicits a number of defensive reflexes, including cough, altered breathing pattern, and altered autonomic drive, which are important for normal lung homeostasis. However, diseases that afflict the lung are associated with altered reflexes, resulting in a variety of symptoms, including increased cough, dyspnea, airways obstruction, and bronchial hyperresponsiveness. This review summarizes the current knowledge concerning the physiological role of different sensory nerve subtypes that innervate the lung, the factors which lead to their activation, and pharmacological approaches that have been used to interrogate the function of these nerves. This information may potentially facilitate the identification of novel drug targets for the treatment of respiratory disorders such as cough, asthma, and chronic obstructive pulmonary disease.

Inhibition of Leptin Regulation of Parasympathetic Signaling as a Cause of Extreme Body Weight-Associated Asthma

“…We observed that M 2 and M 3 muscarinic receptors (M 2 R and M 3 R) are the most highly expressed (Figure 4E) and that they both localize to ASM cells and the airway epithelium (Figure S4J) (Coulson and Fryer, 2003; Fisher et al, 2004). Signaling through M 2 R exerts an inhibitory role in prejunctional parasympathetic nerve terminals by preventing Ach release (Canning and Spina, 2009; Coulson and Fryer, 2003). Consistent with this notion, M 2 R − / − mice showed an increase in R and Rn at baseline (Figure 4F), thus distinguishing signaling through this receptor from leptin regulation of bronchodilation.…”

Airway smooth muscle in airway reactivity and remodeling: what have we learned?

“…In airway diseases such as asthma and bronchitis, airway hyperresponsiveness can be modulated by increased cholinergic outflow from the parasympathetic nervous system (34,276,315). Design for reflex protection of the airway via bidirectional central nervous system (CNS)-airway pathways, repeated exposures to environmental pollutants, inflammatory stimuli, and other noxious agents may modulate afferent airway sensory pathways (150,315,316), leading to increased excitability of airway-related vagal preganglionic neurons and airway hyperresponsiveness.…”

“…The relevance of the complex neural pathways lies in their enhanced contribution in airway diseases, for example in allergen-induced changes in ASM tone and mucous secretion due to increased activation of preganglionic airway parasympathetic nerves (neurogenic asthma) (34,276,315), and the fact that commonly used drugs such as ipratropium target cholinergic innervation in preventing excessive bronchoconstriction. However, new mechanisms by which neural control of ASM is dynamically modulated are continuing to be identified, highlighting novel pathways for pharmacological intervention.…”

Silencing Nociceptor Neurons Reduces Allergic Airway Inflammation

“…Airway nociceptors respond to chemical, mechanical or thermal stimuli to initiate essential protective airway reflexes such as cough (Canning et al, 2006). Asthmatic patients have a denser network of these fibers around small airways (Barnes, 1996; Myers et al, 2002) and a reduced activation threshold in response to airborne irritants (Canning and Spina, 2009). Patients also display elevated neuropeptide levels in bronchoalveolar lavage fluids (BALF) (Lilly et al, 1995).…”