The Involvement Of Sensory Neuropeptides In Airway Hyper-Responsiveness In Rabbits Sensitized And Challenged To Parietaria Judaica

Background C-fibres have received considerable attention in the context of airway hyper-responsiveness (AHR), in fact several lines of evidence suggest that tachykinins might be involved in the pathogenesis of AHR,Objective The aim of this study was to investigate the role of capsaicin-sensitive sensory C-fibres and tachykinins in rabbits sensitized to the major allergen of Parietaria judaica pollen (Par j1).Methods Airway responsiveness was determined by exposing sensitized rabbits to cumulative concentrations of aerosolized histamine before and after an allergic challenge and after a pretreatment with either vehicle or capsaicin or tachykinin receptor antagonists. Bronchoalveolar lavage was performed following histamine challenge and total and differential cell counts were performed.Results In sensitized rabbits, an AHR to inhaled histamine was observed 24 h after a Par j1 challenge. Capsaicin pre-treatment inhibited the AHR achieved 24 h following antigen exposure (P<0.01). Pre-treatment with the tachykinin NK2, receptor antagonist, SR 48968, significantly reduced the antigen-induced AHR (P < 0.05) while pre-treatment with tachykinin NK1, (SR 140333) and NK3 (SR 142801) receptor antagonists did not significantly modify it. Bronchoalveolar lavage fluid obtained from vehicle and capsaicin-treated rabbits challenged with Par j1 exhibited no significant differences in total and differential cell counts,Conclusions Parietaria judaica-induced AHR in immunized rabbits was shown to be inhibited by pre-treatment with capsaicin, an effect that is not related to an action on the associated pulmonary infiltration of eosinophils. The involvement of NK2 receptor stimulation in this phenomenon also suggests that NK2 receptor antagonists may be useful for investigating mechanisms of bronchopulmonary alterations in asthmatic patients.