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- Title
Reproducibility of the capsaicin-induced dermal blood flow response as assessed by laser Doppler perfusion imaging.
- Authors
Van der Schueren, B. J.; de Hoon, J. N.; Vanmolkot, F. H.; Van Hecken, A.; Depre, M.; Kane, S. A.; De Lepeleire, I.; Sinclair, S. R.
- Abstract
What is already known about this subject • Capsaicin rapidly produces local neurogenic inflammation (characterized by oedema and erythema) when locally administered to the human skin by binding to the TRPV1 receptor present on dermal sensory nerve endings. • In nonhuman primates, a pharmacodynamic assay has been described and validated using capsaicin-induced dermal vasodilation measured by laser Doppler perfusion imaging to assess calcitonin gene-related peptide antagonist activity. • Laser Doppler perfusion imaging has also been shown to be a reliable method for characterizing microvascular changes in the human skin. What this study adds • Capsaicin induces a reproducible within-subject arm-to-arm increase in dermal blood flow (DBF) when applied to the human skin. • This is the first study to describe a non-invasive pharmacodynamic model in humans using capsaicin-induced neurogenic inflammation and allowing repeated, reproducible measurements of DBF to be performed. • This model might therefore be utilized in the early clinical evaluation of antagonists of putative mediators involved in capsaicin-induced dermal vasodilation. Aims 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 µg 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 µg capsaicin was applied on the proximal forearm and changes in DBF assessed up to 30 min ( t30). DBF response was expressed as percent change from baseline ± SD and the corresponding AUC0−30. Reproducibility assessment included calculation of the concordance correlation coefficient (CCC). Results Part I ( n = 12 subjects): compared with placebo, 300 and 1000 µg 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 ≥ 0.8, i.e. substantial to almost perfect reproducibility). In part II ( n = 11), t30 averaged 390 ± 120% and arm-to-arm reproducibility was almost perfect (CCC = 0.91) for AUC0−30. 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.
- Subjects
CAPSAICIN; PHARMACODYNAMICS; BLOOD flow; MICROCIRCULATION disorders; VASODILATION; LASER Doppler blood flowmetry
- Publication
British Journal of Clinical Pharmacology, 2007, Vol 64, Issue 5, p580
- ISSN
0306-5251
- Publication type
Article
- DOI
10.1111/j.1365-2125.2007.02939.x