An inexpensive system for evaluating the tussive and anti-tussive properties of chemicals in conscious, unrestrained guinea pigs

Abstract

Introduction: Commercial whole-body plethysmography systems used to evaluate the anti-tussive potential of drugs employ sophisticated technology, but these systems may be cost prohibitive for some laboratories. The present study describes an alternative, inexpensive system for evaluating the tussive and anti-tussive potential of drugs in conscious, unrestrained guinea pigs. Methods: The system is composed of a transparent small animal anesthesia induction box fitted with a microphone, a camera and a pneumotachometer to simultaneously capture audio, video, air flow and air pressure in real time. Data acquisition and analysis was performed using free software for audio and video, and a research pneumotach system for flow and pressure. System suitability testing was performed by exposing conscious, unrestrained guinea pigs to nebulized aqueous solutions of a selective agonist for TRPV1 (citric acid) or a selective agonist for TRPA1 (AITC), with or without pre-treatment with a selective antagonist for TRPV1 (BCTC) or a selective antagonist for TRPA1 (HC-030031). Results: The system easily discerned coughs from other respiratory events like sneezes. System suitability test results are as follows: AITC caused 10.7 (SEM = 1.4592) coughs vs. 5.8 (SEM = 1.6553) when pre-treated with HC-030031 (P < 0.05). Citric acid caused 12.4 (SEM = 1.4697) coughs vs. 3.2 (SEM = 1.3928) when pre-treated with BCTC (P < 0.002). Discussion: We have described in detail an inexpensive system for evaluating the tussive and anti-tussive potential of chemicals in conscious, unrestrained guinea pigs. Suitability testing indicates that the system is comparable to a commercial whole-body plethysmography system for detecting and differentiating between coughs and sneezes. This system may provide some investigators a cost-conscious alternative to more expensive commercial whole-body plethysmography systems.

Introduction

Coughing serves to maintain the airways free of foreign material and prevent harmful substances from penetrating deeper into the respiratory passages. Coughing can be acute or chronic. Although an acute cough is not considered serious it remains the primary reason individuals seek doctor's counsel. In contrast to an acute cough, a chronic cough is often the result of a more serious underlying medical condition and can be debilitating leading to a poor quality of life. The most effective anti-tussive drugs for treating chronic cough are opioids, but these drugs can lead to physical dependence, respiratory depression and gastrointestinal distress (Belvisi & Geppetti, 2004). Individuals worldwide continue to spend billions of dollars annually on over-the-counter anti-tussive medications (Birring, 2009) despite a systematic review of randomized controlled trials in adults indicating that these medications showed minimal benefits that were of doubtful clinical relevance (Schroeder & Fahy, 2002). Consequently, there is a tremendous unmet clinical need to develop more efficacious anti-tussive agents with greater safety profiles (Dicpinigaitis, 2011).

Whole-body plethysmography is a useful tool for evaluating the potential for chemicals to induce coughing and for the evaluation of the efficacy of anti-tussive drugs in conscious, unrestrained animals. Although commercial whole-body plethysmography systems employ state-of-the-art technology, these systems are expensive and may be cost prohibitive for some research laboratories. This is especially true for laboratories at smaller academic institutions where funding tends to be less than at larger institutions. This may also be true for laboratories in industry that do not have an active anti-tussive research and development program or do not perform respiratory safety pharmacology evaluations, but require a whole-body plethysmography system to support an isolated project where the purchase price of a commercial whole-body plethysmography system cannot be justified. The present study describes an alternative, inexpensive system for evaluating the potential for chemicals to induce coughing and for evaluating the efficacy of anti-tussive drugs in conscious, unrestrained guinea pigs.