Reasearch Awards nomination

Email updates

Keep up to date with the latest news and content from Cough and BioMed Central.

Open Access Research

Fentanyl enhances the excitability of rapidly adapting receptors to cause cough via the enhancement of histamine release in the airways

Junzo Kamei*, Yuki Nakanishi, Megumi Asato and Hiroko Ikeda

Author Affiliations

Department of Pathophysiology and Therapeutics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa, Tokyo 142-8501, Japan

For all author emails, please log on.

Cough 2013, 9:3  doi:10.1186/1745-9974-9-3

Published: 1 February 2013

Abstract

Background

Although the mechanism of fentanyl-induced cough is unclear, several lines of evidence suggest that allergic mediators, such as histamine, may play a role in the production of fentanyl-induced coughs. The aim of this study was to explore the effects of fentanyl on cough sensitivity to inhaled citric acid and on histamine release in BALF in mice.

Methods

The cough reflex was induced by the inhalation of citric acid. Male ICR mice were exposed to a nebulized solution of citric acid at a concentration of 0.1 M under conscious and identical conditions using a body plethysmograph. The number of coughs produced per 3-min period of exposure to citric acid was counted. Histamine content in BALF was analyzed by HPLC post-column derivatization and fluorescence detection.

Results

Intravenous administration of fentanyl increased the number of citric acid-induced coughs. The fentanyl-induced enhancement of the number of citric acid-induced coughs was abolished in mice that had been pretreated with moguisteine, a rapidly adapting receptor (RAR) antagonist or fexofenadine, a histamine H1 receptor antagonist. Fentanyl significantly increased the concentration of histamine in BALF.

Conclusion

The results of this study suggest that fentanyl enhances the excitability of RARs to cause cough, and enhancement of histamine release in the airways may some how be related to this change.