Cough is a common and important symptom of asthma and allergic rhinitis. Previous experimental evidence has shown enhanced cough sensitivity during early phase of experimental allergic rhinitis in guinea pigs. We hypothesized that airway inflammation during the late phase response after repeated nasal antigen challenge may affect the afferent sensory nerve endings in the larynx and tracheobronchial tree and may also modulate cough response. In the present study we evaluated the cough sensitivity during a period of early and late allergic response in sensitized guinea pigs after repeated nasal antigen challenges. Forty-five guinea pigs were sensitized with ovalbumin (OVA). Four weeks later 0.015 ml of 0.5 % OVA was intranasally instilled to develop a model of allergic rhinitis that was evaluated from the occurrence of typical clinical symptoms. Animals were repeatedly intranasally challenged either by OVA (experimental group) or by saline (controls) in 7-day intervals for nine weeks. Cough was elicited by inhalation of citric acid aerosols. Cough was evaluated at 1 or 3 h after the 6th nasal challenge and 17 or 24 h after the 9th nasal challenge. The cough reflex was significantly increased at 1 and 3 h after repeated nasal challenge in contrast to cough responses evoked at 17 and 24 h after repeated nasal challenge. In conclusion, enhanced cough sensitivity only corresponds to an early allergic response after repeated nasal challenges.
Clinical studies showed that GABAB receptor agonists improve symptoms in patients with gastroesophageal reflux disease. One proposed mechanism of this effect is direct inhibition of the gastroesophageal vagal tension mechanosensors by GABAB agonists leading to reduction of reflux. In addition to tension mechanosensors, the vagal nodose ganglion supplies the esophagus with nociceptive C-fibers that likely contribute to impairment of esophageal reflex regulation in diseases. We hypothesized that GABAB agonists inhibit mechanically-induced activation of vagal esophageal nodose C-fibers in baseline and/or in sensitized state induced by inflammatory mediators. Ex vivo extracellular recordings were made from the esophageal nodose C-fibers in the isolated vagally-innervated guinea pig esophagus. We found that the selective GABAB agonist baclofen (100- 300 μM) did not inhibit activation of esophageal nodose C-fibers evoked by esophageal distention (10-60 mmHg). The mechanical response of esophageal nodose C-fibers can be sensitized by different pathways including the stimulation of the histamine H1 receptor and the stimulation the adenosine A2A receptor. Baclofen failed to inhibit mechanical sensitization of esophageal nodose Cfibers induced by histamine (100 μM) or the selective adenosine A2A receptor agonist CGS21680 (3 nM). Our data suggest that the direct mechanical inhibition of nodose C-fibers in the esophagus is unlikely to contribute to beneficial effects of GABAB agonists in patients with esophageal diseases., M. Brozmanová, ... [et al.]., and Obsahuje seznam literatury