Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat

J Physiol. 2008 Dec 1;586(23):5771-86. doi: 10.1113/jphysiol.2008.161042. Epub 2008 Oct 2.

Abstract

Vagal pulmonary myelinated afferents are normally not activated by capsaicin, a selective agonist of transient receptor potential vanilloid type 1 (TRPV1) receptors. This study was carried out to investigate whether the expression of TRPV1 in these afferents is altered when chronic airway inflammation is induced by ovalbumin (Ova) sensitization. Two groups of Brown-Norway rats (sensitized and control) were exposed to aerosolized Ova and vehicle, respectively, 3 days per week for 3 weeks. After the C-fibre conduction in both vagus nerves was blocked, right-atrial injection of capsaicin elicited augmented breaths in sensitized rats breathing spontaneously, but not in control rats, indicating a stimulation of rapidly adapting receptors (RARs) by capsaicin. Single-unit fibre activities of RARs and slow adapting receptors (SARs), identified by their firing behaviour and adaptation indexes in response to lung inflation, were recorded in anaesthetized, vagotomized and artificially ventilated rats. Capsaicin injection evoked either negligible or no response in both RARs and SARs of control rats. However, in striking contrast, the same dose of capsaicin evoked an immediate stimulatory effect on these myelinated afferents in sensitized rats. Furthermore, the immunohistochemistry experiments showed that there was a significant increase in the proportion of TRPV1-expressing pulmonary neurones in nodose ganglia of sensitized rats; this increase in TRPV1 expression was found mainly in neurofilament-positive (myelinated) neurones. In conclusion, allergen-induced airway inflammation clearly elevated capsaicin sensitivity in myelinated pulmonary afferents, which probably resulted from an increased expression of TRPV1 in these sensory nerves.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Blood Pressure / drug effects
  • Capsaicin / administration & dosage
  • Capsaicin / pharmacology*
  • Ganglia / drug effects
  • Ganglia / metabolism
  • Heart Rate / drug effects
  • Immunohistochemistry
  • Lung / drug effects*
  • Lung / pathology
  • Lung / physiopathology
  • Male
  • Nerve Fibers, Myelinated / drug effects*
  • Nerve Fibers, Myelinated / physiology
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Nodose Ganglion / drug effects
  • Nodose Ganglion / metabolism
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology
  • Rats
  • Rats, Inbred BN
  • Respiration / drug effects
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / metabolism
  • Respiratory Hypersensitivity / physiopathology
  • Sensory System Agents / administration & dosage
  • Sensory System Agents / pharmacology
  • TRPV Cation Channels / agonists
  • TRPV Cation Channels / metabolism*
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology

Substances

  • Sensory System Agents
  • TRPV Cation Channels
  • Trpv1 protein, rat
  • Ovalbumin
  • Capsaicin