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

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

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

Kameietal.Cough2013,9:3 /content/9/1/3 Cough RESEARCH OpenAccess Fentanylenhancestheexcitabilityofrapidly adaptingreceptorstocausecoughviathe enhancementofhistaminereleaseintheairways JunzoKamei*,YukiNakanishi,MegumiAsatoandHirokoIkeda Abstract Background:Althoughthemechanismoffentanyl-inducedcoughisunclear,severallinesofevidencesuggestthat allergicmediators,suchashistamine,mayplayaroleintheproductionoffentanyl-inducedcoughs.Theaimofthis studywastoexploretheeffectsoffentanyloncoughsensitivitytoinhaledcitricacidandonhistaminereleasein BALFinmice. Methods:Thecoughreflexwasinducedbytheinhalationofcitricacid.MaleICRmicewereexposedtoa nebulizedsolutionofcitricacidataconcentrationof0.1Munderconsciousandidenticalconditionsusingabody plethysmograph.Thenumberofcoughsproducedper3-minperiodofexposuretocitricacidwascounted. HistaminecontentinBALFwasanalyzedbyHPLCpost-columnderivatizationandfluorescencedetection. Results:Intravenousadministrationoffentanylincreasedthenumberofcitricacid-inducedcoughs.The fentanyl-inducedenhancementofthenumberofcitricacid-inducedcoughswasabolishedinmicethathadbeen pretreatedwithmoguisteine,arapidlyadaptingreceptor(RAR)antagonistorfexofenadine,ahistamineH1receptor antagonist.FentanylsignificantlyincreasedtheconcentrationofhistamineinBALF. Conclusion:TheresultsofthisstudysuggestthatfentanylenhancestheexcitabilityofRARstocausecough,and enhancementofhistaminereleaseintheairwaysmaysomehowberelatedtothischange. Background and/or allergic mediators, such as histamine and leuko- Fentanyl,asyntheticopioid,isapopularchoiceamongst trienes, may play a role in the production of fentanyl- anesthesiologists because of its quick onset, short dur- inducedcoughs. ation of action, ease of titrability, intense analgesia, car- Wepreviouslyreportedthatalthoughtheinhalationof diovascular stability and low histamine release [1,2]. 0.1Mcitricacidbyitselfproducedonlyafewcoughsin Although opioid agonists are known to possess antitus- guinea pigs, pre-exposure to