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

Clin Exp Allergy. 2004 Sep;34(9):1474-9. doi: 10.1111/j.1365-2222.2004.02066.x.


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 microm), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capsaicin / immunology*
  • Female
  • Immunohistochemistry / methods
  • Ion Channels
  • Mice
  • Mice, Inbred BALB C
  • Nerve Growth Factor / immunology*
  • Neurons, Afferent / immunology*
  • Nodose Ganglion / immunology*
  • Receptor, trkA / analysis
  • Receptor, trkA / immunology
  • Respiratory System / immunology*
  • Respiratory System / innervation
  • Substance P / immunology*
  • TRPV Cation Channels


  • Ion Channels
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Substance P
  • Nerve Growth Factor
  • Receptor, trkA
  • Capsaicin