Topical menthol increases cutaneous blood flow.
Level 2 - randomized trial
Individual randomized controlled experimental human physiological trial
PubMed 27131832 · doi:10.1016/j.mvr.2016.04.010
What was done
Three experimental protocols were conducted to evaluate the microvascular effects and mechanisms of topical menthol and Ilex paraguariensis. Cutaneous red cell flux was measured using laser speckle contrast imaging and normalized to mean arterial pressure as cutaneous vascular conductance (CVC: flux·mmHg⁻¹). Protocol 1 tested placebo, 4% menthol, 0.7% ilex, and combination gels. Protocol 2 modeled a dose-response curve using seven concentrations of menthol (0.04% to 8%). Protocol 3 assessed gels under local thermal control (34°C) with and without sensory nerve blockade (4% lidocaine), alongside post-occlusive reactive hyperemia (PORH) and local heating (42°C).
What was found
Topical menthol significantly increased cutaneous blood flow compared to placebo (3.41 ± 0.33 vs. 1.1 ± 0.19 CVC; p < 0.001). Menthol caused a dose-dependent increase in skin blood flow (main effect, p < 0.05) with an ED50 of 1.0%. Menthol increased blood flow during PORH (3.62 ± 0.29 vs. 2.50 ± 0.21 flux·mmHg⁻¹; p < 0.001) but not during local heating (2.98 ± 0.24 vs. 2.86 ± 0.32 flux·mmHg⁻¹; p = 0.44). Sensory nerve inhibition attenuated menthol-mediated vasodilation at baseline (1.29 ± 0.19 flux·mmHg⁻¹; p < 0.001) and during PORH (2.79 ± 0.28 flux·mmHg⁻¹; p < 0.001), but not during local heating (3.45 ± 0.21 flux·mmHg⁻¹; p = 0.1). Ilex paraguariensis did not alter skin blood flow.
Why it matters
Contrary to the expectation of cooling-induced vasoconstriction, topical menthol acts as a cutaneous vasodilator. This dose-dependent response is mediated partly by sensory nerves and endothelium-derived hyperpolarizing factors rather than nitric oxide pathways.
Limits
The abstract omits sample size, participant demographics (age, sex, health status), and blinding details. Clinical analgesic endpoints were not evaluated.
Cited by
- supports Menthol and eucalyptus compounds bind to cold-sensing TRP receptors on the skin, causing local vasodilation and increased blood flow to generate heat after an initial cold sensation.