Targeting TRP channels for chronic cough: from bench to bedside

Area of Science:

• Neuroscience
• Pharmacology
• Respiratory Medicine

Background:

• Cough is a primary reason for primary care visits in the UK, representing an unmet medical need.
• Existing cough therapies have limited efficacy and potential side effects.
• Excessive cough in diseases like asthma and COPD significantly impacts patients' quality of life.

Purpose of the Study:

• To review the role of transient receptor potential (TRP) ion channels in airway sensory nerve activation and cough reflex.
• To highlight TRP channels as potential therapeutic targets for chronic cough.
• To discuss the clinical utility of TRP channel antagonists as antitussives.

Main Methods:

• Review of current scientific literature on TRP channels and the cough reflex.
• Focus on four key TRP channels: TRPV1, TRPA1, TRPV4, and TRPM8.
• Analysis of expression and function of these channels in airway disease models.

Main Results:

• TRP channels act as cellular sensors in vagal sensory afferents, initiating the cough reflex.
• Activators of TRP channels are present in diseased airways, enhancing cough responses.
• Increased expression of certain TRP channels is observed in airway diseases.

Conclusions:

• TRP channels are promising therapeutic targets for chronic cough.
• TRP channel antagonists demonstrate potential as novel antitussive agents.
• Targeting sensory afferent pathways offers a new avenue for cough treatment.