Background: Nerve growth factor (NGF) is an important mediator of airway hyperresponsiveness and hyperalgesia but its role in cough is unknown.
Objectives: In this study we investigated the effects of NGF on the cough reflex and airway caliber in guinea pigs. We also assessed the involvement of the tropomyosin¬-related kinase A (TrkA) and transient receptor potential vanilloid-1 (TRPV1) receptors, and p38 mitogen activated protein kinase (MAPK) dependent pathway on any NGF-induced effects on cough and airway obstruction.
Methods: Guinea pigs were placed in a transparent whole body plethysmograph box. Cough was assessed visually, acoustically and by analysis of the flow signal. Airway obstruction was measured using enhanced pause (Penh) as an index.
Results: Exposure of guinea pigs to NGF did not induce a cough response nor a significant airway obstruction. However, exposure of guinea pigs to NGF immediately before citric acid inhalation resulted in a significant increase in the citric acid-induced cough and airway obstruction compared to vehicle treated animals. Pre-treatment with the TrkA antagonist, K252a, or the TRPV1 receptor antagonist, iodoresiniferatoxin, significantly inhibited the NGF enhanced cough and airway obstruction. Exposure to NGF also increased p38 MAPK phosphorylation, but pretreatment with the p38 MAPK inhibitor, SB203580, did not affect either the NGF enhanced cough or airway obstruction despite preventing the NGF-induced elevation in p38 MAPK phosphorylation.
Conclusions: The data show that NGF can enhance both cough and airway obstruction via a mechanism that involves the activation of TrkA and TRPV1 receptors but not the p38 MAPK pathway.