Article Title

Ilex Increases Cutaneous Blood Flow by Augmenting Endothelium-derived Hyperpolarizing Factors


Craighead, D., Conlon, C., Alexander, L, FACSM. Penn State University, University Park, PA

Purpose: Menthol containing topical analgesics are used for pain relief and cryotherapy. However, the effect of these topical agents on skin blood flow (SkBF) has not been fully elucidated. We sought to determine the effects of a commercially available analgesic gel, and isolated ingredients menthol, and ilex paraguarensis on nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF)-mediated cutaneous vasodilation. Methods: Standardized reactive hyperemia (RH) and local heating (LH) protocols to investigate EDHF and NO-mediated vasodilation respectively were performed on 10 healthy human subjects. Four gels were applied to separate sites on the ventral forearm: 1) placebo 2) topical analgesic 3) menthol 4) ilex. Temperature at each site was controlled with a local heater. Temperature was clamped at 34⁰C for baseline and RH, increased to 42⁰C for LH, and subsequently increased to 43⁰C to elicit maximal vasodilation. Red blood cell flux was measured using laser speckle contrast imaging and normalized to cutaneous vascular conductance (CVC: flux/mean arterial pressure) and expressed as a percent of maximum CVC (%CVCmax). Results: The topical analgesic and ilex, but not menthol, caused a baseline increase in %CVCmax compared to placebo. The topical analgesic and ilex also caused an increase in the total hyperemic response (THR). There was no difference in %CVCmax across sites in response to LH. Menthol was not significantly different from placebo.

Conclusion: Menthol had no effect on skin blood flow, however commercially available analgesic gels containing Ilex augments SkBF at baseline and during RH, likely through EDHF-mediated mechanisms.

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