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Nerve growth factor-induced substance P in capsaicin-insensitive vagal neurons innervating the lower mouse airway


Q. Thai Dinh, Department of Internal Medicine and Clinical Research Unit of Allergy, Charité-Humboldt University, Ostring 3, R. 3.0066, Augustenburger Platz 1, D-13353 Berlin, Germany.


Background Nerve growth factor (NGF) is elevated in allergic diseases such as bronchial asthma and can lead to an induction of substance P (SP) and related neuropeptides in guinea-pigs large-diameter, neurofilament-positive airway neurons.

Objective In the present study, the effect of NGF on tyrosine kinase receptor trkA and the capsaicin receptor TRPV1 expression in airway-specific vagal sensory neurons located in the jugular–nodose ganglia complex (JNC) of mice was investigated.

Methods Using retrograde neuronal tracing in combination with double-labelling immunohistochemistry, SP, trkA- and TRPV1-receptor expression was examined in airway-specific sensory neurons of BALB/c mice before and after NGF treatment.

Results NGF injected into the lower airway was able to induce SP (13.0±2.03% vs. 5.9±0.33%) and trkA expression (78±2.66% vs. 60±2.11%) in larger diameter (>25 μm), capsaicin-insensitive and trkA-positive vagal sensory neurons that were retrograde-labelled with Fast Blue dye from the main stem bronchi.

Conclusion Based on the extent of SP and trkA co-expression in airway-specific neurons by NGF treatment, the present study suggests that, following a peripheral activation of trkA receptor on SP afferent by NGF which is elevated in allergic inflammation, there may be trkA-mediated SP induction to mediate neurogenic airway inflammation.