Airway Vagal Neuroplasticity Associated with Respiratory Viral Infections

Abstract

Respiratory virus infections leads to coughing, sneezing, and increases in reflex parasympathetic bronchoconstriction and secretions. These responses to viral infection are exclusively or largely secondary to changes in the function of the nervous system. For many with underlying airway pathologies such as asthma and COPD, this neuroplasticity can lead to disease exacerbations and hospitalization. Relatively little is understood about the cellular and molecular mechanisms that underlie the changes in neuronal control of the respiratory tract during viral infection, but the evidence supports the idea that changes occur in the physiology of both the sensory and autonomic innervation. Virus infection can lead to acute increases in the activity of sensory nerves as well as to genetic changes causing alterations in sensory nerve phenotype. In addition, respiratory viral infections are associated with changes in the control of neurotransmitter release from cholinergic nerve endings terminating at the level of the airway smooth muscle.

Neuro–Immune Cell Units: A New Paradigm in Physiology

“…Lung sensory neurons originate in the vagus nerve and lower cervical and upper thoracic spinal dorsal root ganglia (112,113). Sensory innervation is essential for the pulmonary cycle, bronchomotor and vasomotor tones, and mucus secretion (112,120). Sensory nerves also initiate respiratory sensations and reflexes (coughing and sneezing) in pathologic conditions (112).…”

“…Additionally, there is evidence for the control of inflammation by peptidergic sensory neurons. For example, during viral infection, increased activity in sensory and autonomic innervation leads to the urge to cough (120). Nociceptor activation was also shown to induce the release of neuropeptides involved in recruitment and activation of immune cells (64,121).…”

Addressing unmet needs in understanding asthma mechanisms

“…Neuronal dysfunction in asthma can be amplified by respiratory viral infections [406], but this is an area that requires further investigation to determine the degree to which this is important in man.…”

Mechanisms and Biomarkers of Exercise-Induced Bronchoconstriction

“…These sensory neurons send signals centrally, leading to a coordinated response with the efferent parasympathetic nervous system (see below), as well as through a local reflex called retrograde axonal transmission. It is becoming increasingly clear that airway hyperresponsiveness (AHR) is mediated through alterations in both the sensory and autonomic nervous system pathways in the airways (91). This neural plasticity in asthma is the result of changes in the composition of the different types of sensory neurons, the production of neurokinins, such as neurokinin A (NKA) and substance P (SP), and the density of transient receptor potential (TRP) channels, such as TRP vanilloid receptor 1 (TRPV1) which serves as the receptor for capsaicin.…”