title: Blockade of airway sensory nerves and dyspnea in humans.
abstract: Evidence has accumulated from previous studies that vagal fibers in the lungs are involved in the genesis of dyspnea. In a series of human studies, based on our previous animal data (J Physiol 1998; 508:109-18; J Appl Physiol 1998; 84:417-24; J Appl Physiol 2003; 95:1315-24) we established that intravenous adenosine has a dyspnogenic effect (J Appl Physiol 2005; 98:180-5; Respir Res 2006; 7:139; Pulm Pharmacol Ther 2008; 21:208-13), strongly implicating a role for vagal C-fibers in the genesis of dyspnea. We have now analyzed the relative effects of blockade of vagal C-fibers by two methods and routes of delivery: by inhibition of the sodium channel and interruption of action potential conduction in the nerve by inhaled local anesthetic (lidocaine), and by blockade by systemic theophylline, a known, nonselective adenosine receptor antagonist. Both techniques significantly (p < 0.05) attenuated the dyspneic response to intravenous adenosine. However, the attenuation was significantly (p < 0.05) greater with pretreatment with systemic theophylline (mean change in response, DeltaAUC -44%) versus pretreatment with inhaled lidocaine (mean change in response, DeltaAUC -11.8%). These differences in the results of airway sensory nerve blockade probably reflect different populations of C fiber receptors and may explain conflicting results of previous studies of dyspnea and airway anesthesia.
authors.affiliation: Division of Pulmonary Medicine - MC1321, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06030-1321, USA. nburki@uchc.edu
authors.forename: Nausherwan K
authors.initials: NK
authors.lastname: Burki
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000779:Anesthetics, Local / Q000494:pharmacology; D004311:Double-Blind Method; D004417:Dyspnea / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009407:Nerve Block / Q000379:methods; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000779:Anesthetics, Local; D058915:Purinergic P1 Receptor Antagonists; D015222:Sodium Channels; D008012:Lidocaine; D013806:Theophylline