title: Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging.
abstract: OBJECTIVE
  Part I: to establish the dose and appropriate application site of capsaicin on the human forearm in order to produce a robust and reproducible dermal blood flow (DBF) response. Part II: to evaluate the within-subject arm-to-arm and period-to-period reproducibility.
  
  
  METHODS
  Both parts consisted of two study visits. In part I, placebo and 100, 300 and 1000 microg capsaicin were applied at four predefined sites on the volar surface of both forearms. Placebo and capsaicin doses were randomized and balanced by site between subjects. Changes in DBF were assessed by laser Doppler perfusion imaging up to 60 min after capsaicin application. In part II, only 1000 microg capsaicin was applied on the proximal forearm and changes in DBF assessed up to 30 min (t(30)). DBF response was expressed as percent change from baseline +/- SD and the corresponding AUC(0-30). Reproducibility assessment included calculation of the concordance correlation coefficient (CCC).
  
  
  RESULTS
  Part I (n = 12 subjects): compared with placebo, 300 and 1000 microg capsaicin increased DBF (P < 0.05) at all time points except at 10 min. This increase was reproducible at the two most proximal sites from the 30-min time point onwards when compared between arms (CCC >or= 0.8, i.e. substantial to almost perfect reproducibility). In part II (n = 11), t(30) averaged 390 +/- 120% and arm-to-arm reproducibility was almost perfect (CCC = 0.91) for AUC(0-30).
  
  
  CONCLUSIONS
  Capsaicin induces a reproducible within-subject arm-to-arm increase in DBF. We provide a non-invasive pharmacodynamic model in humans to test antagonists of mediators involved in capsaicin-induced dermal vasodilation, including calcitonin gene-related peptide antagonists.
authors.affiliation: Center for Clinical Pharmacology, University Hospital Gasthuisberg (K.U. Leuven), Leuven, Belgium. bart.vanderschueren@uz.kuleuven.be
authors.forename: B J
authors.initials: BJ
authors.lastname: Van der Schueren
authors.forename: J N
authors.initials: JN
authors.lastname: de Hoon
authors.forename: F H
authors.initials: FH
authors.lastname: Vanmolkot
authors.forename: A
authors.initials: A
authors.lastname: Van Hecken
authors.forename: M
authors.initials: M
authors.lastname: Depre
authors.forename: S A
authors.initials: SA
authors.lastname: Kane
authors.forename: I
authors.initials: I
authors.lastname: De Lepeleire
authors.forename: S R
authors.initials: SR
authors.lastname: Sinclair
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D015203:Reproducibility of Results; D018689:Sensory System Agents / Q000494:pharmacology*; D012867:Skin / Q000098:blood supply*; D016896:Treatment Outcome
chemical_list: D010879:Piperazines; D011799:Quinazolines; D018689:Sensory System Agents; D002211:Capsaicin; C406305:olcegepant