Neuronal Regulation of Airway Smooth Muscle Activity

The contractile state of airway smooth muscle is governed by an intricate interplay between autonomic and sensory nerves. Parasympathetic efferents release acetylcholine to induce bronchoconstriction via muscarinic receptors on smooth muscle, while sympathetic pathways modulate relaxation through adrenergic receptors. Pre-junctional M2 muscarinic autoreceptors temper acetylcholine release and thus restrain excessive constriction. Concurrently, sensory (afferent) fibres detect chemical and mechanical stimuli in the airway mucosa and convey signals centrally, triggering reflex arcs that adjust tone, cough and secretion. These fibres also release neuropeptides such as substance P and calcitonin gene-related peptide locally, amplifying smooth muscle contraction and inflammatory responses. In disease states such as asthma and chronic cough, inflammatory mediators and environmental insults reshape neuronal function—enhancing excitability, altering receptor expression and promoting nerve growth—to drive airway hyperreactivity. Emerging evidence implicates ion channels, including acid-sensing and transient receptor potential receptors, in sensory neuron activation under acidic or allergenic conditions. Together, these neuronal circuits establish a dynamic regulatory network that determines airway calibre under physiological and pathological conditions and represents a rich source of therapeutic targets for obstructive airway diseases.

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Neuronal Regulation of Airway Smooth Muscle Activity publication trend

The graph below shows the total number of articles in neuronal regulation of airway smooth muscle activity across all publications each year (not limited to Nature Index journals).

Technical terms

Parasympathetic nervous system: The branch of the autonomic nervous system that promotes bronchoconstriction and mucus secretion via cholinergic fibres.

M2 muscarinic receptor: A pre-junctional autoreceptor on parasympathetic nerves that limits acetylcholine release.

Afferent (sensory) nerve: A neuron that transmits chemical or mechanical stimuli from the airway to the central nervous system.

Bronchoconstriction: Narrowing of airway diameter due to smooth muscle contraction.

Substance P: A neuropeptide released by sensory nerves that enhances smooth muscle contraction and vascular permeability.

Acid-sensing ion channel (ASIC): A proton-gated cation channel expressed by sensory neurons activated under acidic conditions.

Airway hyperreactivity (AHR): Exaggerated bronchoconstrictive response to stimuli characteristic of asthma.

Neuronal plasticity: The capacity of nerves to change structure, function or gene expression in response to environmental or inflammatory cues.

References

1. Acid-Sensing Ion Channel 1a Contributes to Airway Hyperreactivity in Mice. PLOS ONE (2016).
2. Airway Sensory Nerve Plasticity in Asthma and Chronic Cough. Frontiers in Physiology (2021).
3. Dual p38/JNK Mitogen Activated Protein Kinase Inhibitors Prevent Ozone-Induced Airway Hyperreactivity in Guinea Pigs. PLOS ONE (2013).