DOSE-DEPENDENT EFFECTS OF CAPSAICIN NASAL CHALLENGE - IN-VIVO EVIDENCE OF HUMAN AIRWAY NEUROGENIC INFLAMMATION

Background: Nerve involvement has been implicated in the pathophysiolo gy of chronic respiratory inflammatory diseases. Peptidergic nerve sti mulation has been shown to induce leukocyte activation and plasma extr avasation in the airways of various animal species. The occurrence of this phenomenon of neurogenic inflammation in the human airway, howeve r, has not been established. Objective: We conducted this study to det ermine whether neuronal stimulation can induce reproducible and dose-d ependent inflammatory changes in the human upper airway. Methods: Ten volunteers with active allergic rhinitis participated in the study. Ca psaicin, the pungent component of hot pepper that specifically stimula tes afferent nerve fibers, was administered by means of nasal spray in doses of 1 mu g, 10 mu g, and 100 mu g in a double-blind, randomized, crossover manner with 1 week between doses. Symptom scores before and after capsaicin nasal challenge were recorded by using visual analog scales. Nasal lavage fluids collected before and at 30 minutes, 1 hour , and 4 hours after capsaicin challenge were analyzed for leukocyte co unts; albumin and lysozyme levels were measured to evaluate effects on plasma leakage and gland secretion, respectively. Results: Capsaicin nasal challenge produced symptoms of burning, congestion, and rhinorrh ea. Leukocyte counts or albumin and lysozyme levels were not significa ntly increased after administration of 1 mu g of capsaicin at any time point. On the other hand, there were significant increases in leukocy te counts 1 hour (p < 0.05) and 4 hours (p = 0.008) after 10 mu g of c apsaicin and 30 minutes (p = 0.009), 1 hour (p = 0.007), and 4 hours ( p = 0.007) after 100 mu g of capsaicin. Albumin and lysozyme levels we re both significantly in creased 30 minutes after 10 mu g and 100 mu g of capsaicin (p = 0.005 for both). Comparison of changes in symptom s cores, leukocyte counts, and albumin and lysozyme levels among the thr ee capsaicin challenges indicated generally increasing effects with hi gher capsaicin doses. Conclusion: Capsaicin-sensitive nerve stimulatio n in subjects with active allergic rhinitis produces reproducible and dose-dependent leukocyte influx, albumin leakage, and glandular secret ion. These results provide in vivo evidence for the occurrence of neur ogenic inflammation in the human upper airway with active allergic dis ease.