Hyperthermia increases sensitivity of pulmonary C-fibre afferents in rats

J Physiol. 2005 May 15;565(Pt 1):295-308. doi: 10.1113/jphysiol.2005.084319. Epub 2005 Mar 10.


This study was carried out to investigate whether an increase in tissue temperature alters the excitability of vagal pulmonary C-fibres. Single-unit afferent activities of 88 C-fibres were recorded in anaesthetized and artificially ventilated rats when the intrathoracic temperature (T(it)) was maintained at three different levels by isolated perfusion of the thoracic chamber with saline: control (C: approximately 36 degrees C), medium (M: approximately 38.5 degrees C) and high (H: approximately 41 degrees C), each for 3 min with 30 min recovery. Our results showed: (1) The baseline fibre activity (FA) of pulmonary C-fibres did not change significantly at M, but increased drastically (>5-fold) at H. (2) The C-fibre response to right-atrial injection of capsaicin (0.5 microg kg(-1)) was markedly elevated at H (deltaFA = 5.94 +/- 1.65 impulses s(-1) at C and 13.13 +/- 2.98 impulses s(-1) at H; P < 0.05), but not at M. Similar increases in the C-fibre responses to other chemical stimulants (e.g. adenosine, etc.) were found at H; all the enhanced responses returned to control in 30 min. (3) The C-fibre response to lung inflation was also significantly potentiated at H. In sharp contrast, there was no detectable change in either the baseline activity or the responses to lung inflation and deflation in 10 rapidly adapting pulmonary receptors and 10 slowly adapting pulmonary receptors at either M or H. (4) The enhanced C-fibre sensitivity was not altered by pretreatment with indomethacin or capsazepine, a selective antagonist of the transient receptor potential vanilloid type 1 (TRPV1) receptor, but was significantly attenuated by ruthenium red that is known to be an effective blocker of all TRPV channels. (5) The response of pulmonary C-fibres to a progressive increase in T(it) in a ramp pattern further showed that baseline FA started to increase when T(it) exceeded 39.2 degrees C. In conclusion, a pronounced increase in the baseline activity and excitability of pulmonary C-fibres is induced by intrathoracic hyperthermia, and this enhanced sensitivity probably involves activation of temperature-sensitive ion channel(s), presumably one or more of the TRPV receptors, expressed on the C-fibre endings.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology
  • Body Temperature / physiology*
  • Body Temperature Regulation / physiology
  • Hyperthermia, Induced / methods*
  • Ion Channels / metabolism*
  • Lung / innervation*
  • Lung / physiology*
  • Mechanotransduction, Cellular / physiology
  • Neurons, Afferent / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • TRPV Cation Channels
  • Vagus Nerve / physiology*


  • Ion Channels
  • TRPV Cation Channels
  • Trpv1 protein, rat