Signs and Symptoms of Chest Diseases: Cough |

A TRPM8 Agonist Ax-8 Inhibits Capsaicin-Induced Cough in Guinea Pig FREE TO VIEW

Peijian Dong; Yan Huang, MD; Qinxian Wei; Xinyu Wang; Chunli Liu; TakFung Wei
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The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A545. doi:10.1016/j.chest.2016.02.569
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: This study is aim to evaluate A TRPM8 agonist Ax-8 in a standardized guinea pig model of cough.

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 N=10 per group.

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

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