Regulating cough through modulation of sensory nerve function in the airways

Area of Science:

• Respiratory Medicine
• Neuroscience
• Pharmacology

Background:

• Local anesthetics can suppress cough but have dose-limiting side effects.
• Airway afferent nerves, including C-fibres and Aδ fibres, are implicated in cough reflex pathways.
• Targeting these specific nerve subtypes presents a potential therapeutic strategy for chronic cough.

Purpose of the Study:

• To explore novel therapeutic approaches for chronic cough by targeting specific airway afferent nerve subtypes.
• To review the evidence for C-fibres and Aδ fibres in cough and their potential as drug targets.
• To discuss the challenges in translating preclinical findings into effective clinical treatments for cough.

Main Methods:

• Review of existing preclinical and clinical evidence on airway afferent nerves and cough.
• Analysis of the roles of C-fibres (TRPV1, sodium channels) and Aδ fibres in cough.
• Discussion of challenges in preclinical modeling and clinical trial design for anti-tussive drugs.

Main Results:

• C-fibres, targeted by capsaicin, are traditionally studied for cough, with some drugs showing preclinical efficacy.
• Aδ fibres, linked to a specific citric acid-provoked cough receptor, are gaining research interest.
• Inflammation can alter Aδ fibre expression of receptors, making them responsive to endogenous activators.

Conclusions:

• Targeting specific airway nerve subtypes (C-fibres, Aδ fibres) holds promise for future chronic cough treatments.
• Significant challenges remain in preclinical model development and clinical trial design for anti-tussive therapies.
• Development of continuous cough monitoring and better patient stratification is needed for effective treatment evaluation.