AIMS: The mechanism of cough hypersensitivity induced by particulate matter 2.5 (PM2.5) still remains elusive. The current study was designed to explore the effect of transient receptor potential vanilloid-1 (TRPV1) on cough hypersensitivity in airway and central nervous system.
MAIN METHODS: The PM2.5-induced chronic cough model of guinea pig was established by exposure to different doses of PM2.5 for three weeks. After exposure, the animals were microinjected with TRPV1 agonist, antagonist in the dorsal vagal complex respectively. Cough sensitivity was measured by determining the provocative concentration of citric acid inducing 5 or more coughs (C5). Airway inflammation was detected by hematoxylin eosin (HE) staining and Evans blue fluorescence, and substance P (SP) and TRPV1 expressions in airway were observed by immunohistochemical staining. TRPV1 expressions in the dorsal vagal complex were observed by immunofluorescence. Retrograde tracing by pseudorabies virus-Bartha (PRV-Bartha) was conducted to confirm the regulatory pathway between airway and central nervous system.
KEY FINDINGS: PM2.5 induced TRPV1 expressions in both of airway and dorsal vagal complex and airway neurogenic inflammation. Microinjecting agonist and antagonist of TRPV1 into the dorsal vagal complex could induce SP expressions increase and decrease respectively which indicated that TRPV1 in the dorsal vagal complex could promote airway neurogenic inflammation and regulate the cough reflex sensitivity through neural pathways of vagal complex-airways.
SIGNIFICANCE: These findings implicated the therapeutic potential of specific inhibition of TRPV1 in airway and central nervous system for chronic cough induced by PM2.5.