Effect of Transient Receptor Potential Vanihoid-1(TRPV1) From Central Nervous System (CNS) on Guinea Pigs With Chronic Cough Induced by PM2.5

SESSION TITLE: Asthma III SESSION TYPE: Original Investigation Poster PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM PURPOSE: To investigate the effect of TRPV1 from CNS on guinea pigs with chronic cough induced by PM2.5 METHODS: The models of guinea pigs exposed to PM2.5 for 21 days were established and followed by the evaluation of their cough reflex sensitivity via examining the concentrations of citric acid inducing at least 5 coughs (C5). The changes of inflammatory in the airway were observed by HE staining and airway vascular permeability was detected by Evans blue fluorescence. The expressions of substance P (SP) in the airway which is a neuro-transmitter for airway neurogenic inflammation were observed by immunohistochemistry. The expressions of TRPV1 from Botzinger complex and vagal complex in the medulla oblongata were observed by immunofluorescence. TRPV1 agonist, Capsaicine and TRPV1 antagonist, Capsazepine were respectively micro-injected into the vagal complex in the medulla oblongata and the changes of cough reflex sensitivity and airway neurogenic inflammation were detected afterwards. RESULTS: C5 in the model group was significantly lower (p<0.001) which indicated that cough reflex sensitivity increased after being exposed to PM2.5 for 21 days. The tracheal epithelium in the model group had moderate-severe mucosa edema along with inflammatory cells such as macrophages, neutrophil, eosinophilia observed at mucosa and submucosa, et al. Evans blue fluorescence extravasation under the trachea epithelium in the model group increased compared with that in control group (p<0.05) which suggested the increase of vascular permeability in the model group. The expressions of SP increased and TRPV1 increased (p<0.01, p<0.05 respectively). The cough reflex sensitivity and the expression of SP decreased or increased after the micro-injection of Capsaicine or Capsazepine respectively (p<0.01). CONCLUSIONS: TRPV1 from Botzinger complex and vagal complex in the medulla oblongata could induce the increase of cough reflex sensitivity and has a positive effect on the airway neurogenic inflammation on guinea pigs with chronic cough. CLINICAL IMPLICATIONS: Our study contributed to the theoretical basis and reference for the mechanism of respiratory diseases such as chronic cough, asthma, etc. induced by PM2.5 in haze and provided an experimental basis for the choice of therapeutic targets in relevant diseases clinically. DISCLOSURE: The following authors have nothing to disclose: Haining Lv, Jianliang Yue, Zhe Chen, Senlin Chai, Xu Cao, Jie Zhan, Hui Zhang, Rong Dong, KeFang Lai No Product/Research Disclosure Information