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P2 Characterisation Of Aδ- And C-fibres Innervating Guinea-pig Airways
  1. JJ Adcock,
  2. MA Birrell,
  3. SA Maher,
  4. SJ Bonvini,
  5. ED Dubuis,
  6. MA Wortley,
  7. KE Baker,
  8. MG Belvisi
  1. Imperial College, London, UK

Abstract

Introduction and objectives Activation of afferent fibres from the lungs are involved in the cough reflex. In vitro studies in guinea-pig have demonstrated that there are various sub-types of Aδ-fibres (RAR’s, nociceptive and cough)1 and C-fibres (either nodose or jugular ganglia derived),1,2 however, little is known about their equivalent characteristics in vivo. This study aims to characterise the responsiveness of airway sensory nerves, in vivo, ultimately providing a better insight into understanding the role/contribution of the various types/subtypes of Aδ and C-fibres in airway reflexes such as cough.

Methods Male guinea-pigs were anaesthetized with urethane (i.p. 1.5 g kg-1), paralysed and artificially ventilated via a tracheal cannula. A vagus nerve was isolated: single fibres were identified as originating from Aδ- and C-fibres using several criteria. Action potentials were recorded3 and agents were administered to the airways by aerosol.

Results Fibre-types were classified according to their conduction velocities (Table 1). All C-fibres examined were activated by capsaicin, whereas in the Aδ-fibres studies there were both capsaicin responsive and non-responsive fibres, irrespective of their CV range. All fibres exposed to CA responded strongly. There were marked differences in the responsiveness to the TRPV4 agonist, GSK1016790A: Aδ-fibres from all subgroups responded vigorously, but the C-fibres examined were not activated. Interestingly, administration of hypotonic solutions activated all of the Aδ-fibres, but had no effect on C-fibres. In contrast, all C-fibres responded to the TRPA1 agonist, acrolein, with no effect on Aδ-fibres.

Conclusion Several vagalafferent nerve subtypes have been identified in guinea-pig airways in vivo, although the classification does not appear as obvious to that observed in vitro. It is clear that there is a marked variation in their sensitivity to TRP channel agonists, TRPV1, TRPA1 and TRPV4, which have all been shown to evoke cough in a preclinical model in conscious guinea-pigs. It seems probable, therefore, that the different afferent pathways all regulate cough to a greater or lesser degree depending on the nature of the stimulus and underlying cause of the cough.

References

  1. Canning 2004: J Physiol-557 (2):543–558

  2. Weigand 2012: J Physiol-590, (16):4109–4120

  3. Adcock 2003: Brit J Pharmacol-138:407–416

Abstract P2 Table 1

Characteristics of vagal afferent neuronal subtypes innervating the airways and lungs of guinea pigs in vivo

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