Menthol-induced activation of TRPM8 receptors increases cutaneous blood flow across the dermatome.
Level 2 - randomized trial
Double-blind, placebo-controlled randomized crossover trial in humans
PubMed 34717968 · doi:10.1016/j.mvr.2021.104271
What was done
Fifteen healthy young adults (7 men, 8 women; age 22 ± 1 years) participated in a double-blind, placebo-controlled crossover study. Participants received 3 mL of 5% menthol gel (Biofreeze) or placebo gel applied to an 8 × 13 cm area on the L4 dermatome, with treatments separated by 48 hours. Red blood cell flux was measured using laser Doppler flowmetry at baseline and 30 ± 6 minutes post-application at three sites: the treated site, the contralateral leg within the same dermatome (L4), and an untreated distinct dermatome (L5/S1) serving as an uninnervated control. Cutaneous vascular conductance (CVC = flux / mean arterial pressure) was calculated for each site.
What was found
Baseline CVC showed no significant differences between gels or among sites (p > 0.05). After 30 ± 6 minutes, menthol significantly increased CVC at the direct application site from 0.12 ± 0.02 to 1.36 ± 0.19 flux/mm Hg (p < 0.01), whereas placebo showed no significant change (0.10 ± 0.01 to 0.18 ± 0.04 flux/mm Hg, p = 0.91). At the contralateral L4 dermatome, menthol induced a modest but statistically significant increase in CVC (0.16 ± 0.04 to 0.29 ± 0.06 flux/mm Hg, p < 0.01), while placebo did not (0.11 ± 0.02 to 0.15 ± 0.03 flux/mm Hg, p = 0.41). Neither treatment altered CVC at the control L5/S1 dermatome (p > 0.05 for both).
Why it matters
This study provides physiological evidence that localized topical menthol application induces vasodilation not only locally but also across shared spinal dermatomes via a segmental reflex arc, without causing systemic vascular changes.
Limits
The study had a small sample size (n = 15) restricted entirely to young, healthy individuals (mean age 22), limiting generalizability to older adults or populations with vascular or neurological impairments. Long-term vascular effects, functional clinical outcomes (e.g., pain relief), and direct neural recordings were not assessed.
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