Surfactant cocamide monoethanolamide causes eye irritation by activating nociceptor TRPV1.
2021
BACKGROUND AND PURPOSE Cocamide monoethanolamide (CMEA) is commonly used as a surfactant-foam booster in cosmetic formulations. Upon contact with the eye or other sensitive skin areas, CMEA elicits sting and lasting irritation. We hypothesized a specific molecular interaction with TRPV1 by which CMEA caused eye irritation. EXPERIMENTAL APPROACH Eye irritancy is evaluated using eye-wiping test in rabbit and mouse. Intracellular Ca2+ concentrations and action potentials are measured using Ca2+ imaging and current clamp, respectively. Voltage clamp, site-direct mutagenesis and molecular modeling identify the binding pocket of CMEA on TRPV1. KEY RESULTS CMEA-induced eye irritation is ameliorated by selective ablation of TRPV1 and rodents exhibit much stronger responses to CMEA than rabbits. In trigeminal ganglion neurons, CMEA induces Ca2+ influx and neuronal excitability, effects mitigated by TRPV1 inhibitor and absent in TRPV1 knockout neurons. In HEK-293 cell expressing TRPV1, CMEA increases whole-cell currents by increasing channel open probability (EC50 = 10.2 μM) without affecting TRPV2, 3, 4 and TRPA1 activities. Lauric acid monoethanolamide (LAMEA), the most abundant constituent in CMEA, is the most efficacious and potent TRPV1 activator. LAMEA binds to the capsaicin-binding pocket of TRPV1. Both rabbit TRPV1 that possesses the T550I variant and the human TRPV1T550I mutant exhibit much lower sensitivity to LAMEA. CONCLUSIONS AND IMPLICATION CMEA directly activates TRPV1 to produce eye irritation, and rabbit, the traditional animal model used for eye irritancy test is a poor model for evaluating human eye irritants structurally related to CMEA. Our study identifies potential alternatives to CMEA as non-irritating surfactants.
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