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A TRPM8 Agonist Ax-8 Inhibits Capsaicin-Induced Cough in Guinea Pig
Signs and Symptoms of Chest Diseases SESSION TITLE: Cough SESSION TYPE: Original Investigation Poster PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM
A TRPM8 Agonist Ax-8 Inhibits Capsaicin-Induced Cough in Guinea Pig Peijian Dong Yan Huang MD* Qinxian Wei Xinyu Wang Chunli Liu; and TakFung Wei The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China PURPOSE: This study is aim to evaluate A TRPM8 agonist Ax-8 in a standardized guinea pig model of cough.
RESULTS: Guinea pigs exposed to capsaicin had a cough frequency of 24.8 2.1 [mean SEM] coughs per 10 min observation period. One week later, vehicle delivered into the oropharyngeal region did not influence cough frequency (21.4 2.4 coughs), but Ax-8, 5 mg/mL in saline, delivered at 75 mL per animal, inhibited cough (9.0 2.0 coughs, P < 0.01 Mann-Whitney U test). CONCLUSIONS: The results establish that Ax-8 is effective against capsaicin-induced cough in the guinea pig. CLINICAL IMPLICATIONS: TRPM8 is a prospective target of antitussive drug. DISCLOSURE: The following authors have nothing to disclose: Peijian Dong, Yan Huang, Qinxian Wei, Xinyu Wang, Chunli Liu, TakFung Wei No Product/Research Disclosure Information DOI:
http://dx.doi.org/10.1016/j.chest.2016.02.569
Copyright ª 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
journal.publications.chestnet.org
545A
SIGNS AND SYMPTOMS OF CHEST DISEASES
METHODS: Guinea pigs were placed in a transparent plastic 2 L plethysmography chamber equipped with a bias flow regulator that withdrew air at a rate of 2.5 L/min (Buxco, USA). 2mL of a 0.1mM solution of capsaicin was delivered into the camber using an ultrasonic nebulizer with an output of 0.6 mL/min, delivering an aerosol with an estimated median particle diameter of 0.9 mm (Aerogen, Ireland). Animals were exposed for 10 min. Coughs were counted for the 10 min exposure period. The experiment was visually monitored by the investigator. The baseline frequency of coughing in response to capsaicin was recorded for all animals and 7 days later, animals were anesthetized with diethyl ether. A small animal laryngoscope (Penn Century Inc, USA) was used to place the tip of a microsprayer (Penn Century Inc, USA) syringe in the oral cavity. Vehicle or Ax-8 (5 or 10mg/ml) was administered at 75ul per animal. 10 min after injection, the guinea pigs were exposed to the capsaicin mist and the number of coughs recorded. The three groups each had N¼10 per group.
A TRPM8 Agonist Ax-8 Inhibits Capsaicin-Induced Cough in Guinea Pig Peijian Dong Yan Huang MD* Qinxian Wei Xinyu Wang Chunli Liu; and TakFung Wei The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China PURPOSE: This study is aim to evaluate A TRPM8 agonist Ax-8 in a standardized guinea pig model of cough.
RESULTS: Guinea pigs exposed to capsaicin had a cough frequency of 24.8 2.1 [mean SEM] coughs per 10 min observation period. One week later, vehicle delivered into the oropharyngeal region did not influence cough frequency (21.4 2.4 coughs), but Ax-8, 5 mg/mL in saline, delivered at 75 mL per animal, inhibited cough (9.0 2.0 coughs, P < 0.01 Mann-Whitney U test). CONCLUSIONS: The results establish that Ax-8 is effective against capsaicin-induced cough in the guinea pig. CLINICAL IMPLICATIONS: TRPM8 is a prospective target of antitussive drug. DISCLOSURE: The following authors have nothing to disclose: Peijian Dong, Yan Huang, Qinxian Wei, Xinyu Wang, Chunli Liu, TakFung Wei No Product/Research Disclosure Information DOI:
http://dx.doi.org/10.1016/j.chest.2016.02.569
Copyright ª 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
journal.publications.chestnet.org
545A
SIGNS AND SYMPTOMS OF CHEST DISEASES
METHODS: Guinea pigs were placed in a transparent plastic 2 L plethysmography chamber equipped with a bias flow regulator that withdrew air at a rate of 2.5 L/min (Buxco, USA). 2mL of a 0.1mM solution of capsaicin was delivered into the camber using an ultrasonic nebulizer with an output of 0.6 mL/min, delivering an aerosol with an estimated median particle diameter of 0.9 mm (Aerogen, Ireland). Animals were exposed for 10 min. Coughs were counted for the 10 min exposure period. The experiment was visually monitored by the investigator. The baseline frequency of coughing in response to capsaicin was recorded for all animals and 7 days later, animals were anesthetized with diethyl ether. A small animal laryngoscope (Penn Century Inc, USA) was used to place the tip of a microsprayer (Penn Century Inc, USA) syringe in the oral cavity. Vehicle or Ax-8 (5 or 10mg/ml) was administered at 75ul per animal. 10 min after injection, the guinea pigs were exposed to the capsaicin mist and the number of coughs recorded. The three groups each had N¼10 per group.