title: Physiology and plasticity of putative cough fibres in the Guinea pig.
abstract: Cough is initiated by activation of afferent nerve fibers with rapidly adapting receptors (RAR) that conduct action potentials in the Adelta range. In addition, various stimuli that activate airway unmylenated C-fibres evoke cough reflexes. We have used a vagally innervated, larynx-trachea-bronchus preparation, isolated from guinea pigs, to study the pharmacology of RARs and C-fibres in vitro. In this preparation afferent fibres with the RAR phenotype are exquisitely sensitive to mechanical perturbation of their receptive fields, but are unaffected by a variety of mediators (e.g. prostaglandins, histamine, bradykinin, serotonin) and by capsaicin. By contrast, C-fibres are much less sensitive to mechanical stimulation, but can be activated by capsaicin and bradykinin. Preliminary evidence supports the hypothesis that bradykinin activate C-fibre by stimulating the capsaicin (vanilloid) receptor VR1. Acids activate both C-fibres and RARs. Acids stimulate RAR fibres by a mechanism that is rapidly inactivated. C-fibres are stimulated by both a rapidly inactivating mechanism, as well as a slowly inactivating mechanism. Drugs that block VR1 inhibit the latter mechanism. Airway inflammation substantially increases the mechanical sensitivity of RAR fibres without affecting their adaptive properties. Airway inflammation also causes a phenotypic switch in neuropeptide innervation of the airways that RAR neurons begin to synthesis neurokinins and calcitonin gene related peptide. In non-inflamed animals these peptides are expressed only in C-fibre neurons. Thus, airway inflammation may not only increase the sensitivity of cough fibres, but may also qualitatively change the role played by sensory neuropeptides in cough reflexes.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA. bundem@jhmi.edu
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Undem
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Carr
authors.forename: Marian
authors.initials: M
authors.lastname: Kollarik
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D019343:Citric Acid / Q000494:pharmacology; D003371:Cough / Q000503:physiopathology*; D006168:Guinea Pigs; D009473:Neuronal Plasticity / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D019343:Citric Acid; D002211:Capsaicin; D001920:Bradykinin