Stimulation of distal esophageal afferent neurons with 0.5% capsaicin in immature canines elicits an intense response referred to as the Esophago- Laryngeal Adductor Reflex (ELAR). The ELAR is characterized by hypertension, tachycardia and intense vocal cord adduction which progresses to laryngospasm. The ELAR demonstrates a unique age-dependency that bears important similarities with the age predisposition of apparent life-threatening events, and sudden infant death syndrome. The ELAR is absent in canines under 6 weeks of age, peaks in intensity between 7-19 weeks of age, and wanes with maturity. Previous studies have suggested that substance P is a key neurotransmitter of the ELAR and that the efferent limb of the response is vagally mediated. The afferent limb and the role of the central nervous system in the ELAR are unknown. This proposal further investigates the ELAR in immature canines. The specific objectives of the proposal are: 1. To characterize the response of the airway of immature canines to distal esophageal afferent stimulation. 2. To assess the effect of maturation on the cardiorespiratory and laryngeal responses of distal esophageal nociceptive stimulation 3. To elucidate the afferent neural pathway of the ELAR. 4. To determine the role of the central vagal nuclei in mediating the ELAR. 5. To determine if esophageal acidification induces the ELAR in immature canines with acute esophagitis.
These specific aims will be explored in immature canines by applying 0.5% capsaicin to the distal esophageal mucosa to elicit an ELAR. The airway response of the ELAR (bronchoconstriction, change in respiratory rate, and laryngeal adduction) will be assessed. Esophageal stimulation with 0.5% capsaicin will be repeated every 3 weeks in 6 week old puppies for 15 weeks to characterize the effect of maturation on the intensity of the ELAR response. Transection and denuding studies will clarify the role of the vagus nerve in mediating the afferent limb of the ELAR. The role of the central vagal nuclei in mediating the ELAR will be assessed by comparing the response to distal esophageal nociceptive stimulation with capsaicin before and after chemically antagonizing their substance P NK1 receptors. Finally, the cardiorespiratory response following distal esophageal acidification of an acutely inflamed esophagus will be compared with the ELAR elicited by 0.5% capsaicin stimulation.
