%0 Journal Article
%T Fentanyl enhances the excitability of rapidly adapting receptors to cause cough via the enhancement of histamine release in the airways
%A Junzo Kamei
%A Yuki Nakanishi
%A Megumi Asato
%A Hiroko Ikeda
%J Cough
%D 2013
%I BioMed Central
%R 10.1186/1745-9974-9-3
%X 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£żM 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.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.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.Fentanyl, a synthetic opioid, is a popular choice amongst anesthesiologists because of its quick onset, short duration of action, ease of titrability, intense analgesia, cardiovascular stability and low histamine release [1,2]. Although opioid agonists are known to possess antitussive activity, it is well known that i.v. administration of fentanyl paradoxically induces cough [3-7]. Fentanyl-induced cough may be explosive at times, and may require immediate therapeutic intervention when it undesirably increases intracranial, intraocular or intra-abdominal pressure [5-7]. Although the mechanism of fentanyl-induced cough is unclear, Agarwal et al. reported that pretreatment with salbutamol, beclomethasone or sodium chromoglycate reduced fentanyl-induced coughs [6]. These results strongly suggest that bronchoconstriction and/or allergic mediators, such as histamine and leukotrienes, may play a role in the production of fentanyl-induced coughs.We previously reported that although the
%U http://www.coughjournal.com/content/9/1/3