title: Dose-dependent effects of capsaicin nasal challenge: in vivo evidence of human airway neurogenic inflammation.
abstract: BACKGROUND
  Nerve involvement has been implicated in the pathophysiology of chronic respiratory inflammatory diseases. Peptidergic nerve stimulation has been shown to induce leukocyte activation and plasma extravasation in the airways of various animal species. The occurrence of this phenomenon of neurogenic inflammation in the human airway, however, has not been established.
  
  
  OBJECTIVE
  We conducted this study to determine whether neuronal stimulation can induce reproducible and dose-dependent inflammatory changes in the human upper airway.
  
  
  METHODS
  Ten volunteers with active allergic rhinitis participated in the study. Capsaicin, the pungent component of hot pepper that specifically stimulates afferent nerve fibers, was administered by means of nasal spray in doses of 1 microg, 10 microg, and 100 microg 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 counts; 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 rhinorrhea. Leukocyte counts or albumin and lysozyme levels were not significantly increased after administration of 1 microg of capsaicin at any time point. On the other hand, there were significant increases in leukocyte counts 1 hour (p < 0.05) and 4 hours (p = 0.008) after 10 microg of capsaicin and 30 minutes (p = 0.009), 1 hour (p = 0.007), and 4 hours (p = 0.007) after 100 microg of capsaicin. Albumin and lysozyme levels were both significantly increased 30 minutes after 10 microg and 100 microg of capsaicin (p = 0.005 for both). Comparison of changes in symptom scores, leukocyte counts, and albumin and lysozyme levels among the three capsaicin challenges indicated generally increasing effects with higher capsaicin doses.
  
  
  CONCLUSIONS
  Capsaicin-sensitive nerve stimulation in subjects with active allergic rhinitis produces reproducible and dose-dependent leukocyte influx, albumin leakage, and glandular secretion. These results provide in vivo evidence for the occurrence of neurogenic inflammation in the human upper airway with active allergic disease.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md., USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Sanico
authors.forename: S
authors.initials: S
authors.lastname: Atsuta
authors.forename: D
authors.initials: D
authors.lastname: Proud
authors.forename: A
authors.initials: A
authors.lastname: Togias
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000032:analysis; D001249:Asthma / Q000175:diagnosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002211:Capsaicin / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D009297:Nasal Mucosa / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D009299:Nasal Provocation Tests / Q000379:methods; D009443:Neuritis / Q000139:chemically induced; D012137:Respiratory System / Q000294:innervation; D012220:Rhinitis / Q000175:diagnosis
chemical_list: D000418:Albumins; D009113:Muramidase; D002211:Capsaicin