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.

Keywords: Airway sensory nerves; Brain-derived neurotrophic growth factor; Cough; Nodose; Respiratory virus; TRPV1; Vagal afferent.

Fig. 1

A schematic highlighting the potential effects of viral infection on vagus nerve activity. (I) Viral infection of epithelial cells can lead to release of mediators that stimulate action potential discharge in afferent nerves, thereby alerting the central nervous system. Viral infection can also lead to the production and release of neurotrophic factors that can (II) influence gene expression in the vagal jugular and nodose ganglia in a manner that can lead to relevant phenotypic changes in the airway sensory nerves. (III) Action potentials arriving in the brainstem are integrated, ultimately leading to sensations and to (IV) increases in preganglionic parasympathetic drive. (V) This will increase neurotransmission at the neuro-effector junctions, causing bronchoconstriction and mucus secretion; effects further amplified by inhibition of inhibitory muscarinic autoreceptors. See text for references