Parainfluenza 3-Induced Cough Hypersensitivity in the Guinea Pig Airways

PLoS One. 2016 May 23;11(5):e0155526. doi: 10.1371/journal.pone.0155526. eCollection 2016.

Abstract

The effect of respiratory tract viral infection on evoked cough in guinea pigs was evaluated. Guinea pigs were inoculated intranasally with either parainfluenza type 3 (PIV3) and cough was quantified in conscious animals. The guinea pigs infected with PIV3 (day 4) coughed nearly three times more than those treated with the viral growth medium in response to capsaicin, citric acid, and bradykinin. Since capsaicin, citric acid, and bradykinin evoked coughing in guinea pigs can be inhibited by drugs that antagonize the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), it was reasoned that the virally-induced hypertussive state may involve alterations in TPRV1 activity. PIV3 infection caused a phenotypic switch in tracheal nodose Aδ "cough receptors" such that nearly 50% of neurons began to express, de novo, TRPV1 mRNA. There was also an increase TRPV1 expression in jugular C-fiber neurons as determined by qPCR. It has previously been reported that tracheal-specific nodose neurons express the BDNF receptor TrkB and jugular neurons express the NGF receptor TrkA. Jugular neurons also express the artemin receptor GFRα3. All these neurotrophic factors have been associated with increases in TRPV1 expression. In an ex vivo perfused guinea pig tracheal preparation, we demonstrated that within 8 h of PIV3 infusion there was no change in NGF mRNA expression, but there was nearly a 10-fold increase in BDNF mRNA in the tissue, and a small but significant elevation in the expression of artemin mRNA. In summary, PIV3 infection leads to elevations in TRPV1 expression in the two key cough evoking nerve subtypes in the guinea pig trachea, and this is associated with a hypertussive state with respect to various TRPV1 activating stimuli.

Publication types

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

MeSH terms

  • Animals
  • Cough / genetics
  • Cough / immunology
  • Cough / virology*
  • Gene Expression
  • Guinea Pigs
  • Male
  • Nerve Fibers, Unmyelinated / physiology
  • Nerve Fibers, Unmyelinated / virology
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Nodose Ganglion / immunology
  • Nodose Ganglion / virology
  • Parainfluenza Virus 3, Human / physiology*
  • Paramyxoviridae Infections / complications*
  • Paramyxoviridae Infections / genetics
  • Paramyxoviridae Infections / immunology
  • Paramyxoviridae Infections / virology
  • Respiratory Hypersensitivity / complications
  • Respiratory Hypersensitivity / genetics
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / virology*
  • TRPV Cation Channels / genetics
  • TRPV Cation Channels / metabolism
  • Trachea / immunology
  • Trachea / innervation
  • Trachea / metabolism
  • Trachea / virology

Substances

  • Nerve Growth Factors
  • TRPV Cation Channels