Relationship between sensory irritation on skin surface and TRP channel activation.

Mechanisms underlying sensory irritation caused by chemical stimuli on the skin surface remain unknown. Recently, it has been clarified that TRPA1 and TRPV1 are important for sensing nociceptive and temperature stimuli. This study aimed to clarify the mechanism of hTRPA1 and hTRPV1 in sensory irritation on the skin by evaluating the effects of anti-bacterial agents, ethanol, or polyols using electro-physiological methods in HEK293 cells. Parabens (1 mM) activated hTRPA1 in an alkyl chain length-dependent manner. Conversely, high concentrations (>500 mM) of ethanol and polyols activate hTRPV1. The intensities of sensory irritation caused by anti-bacterial agents or polyols correlated with their abilities to activate TRPA1 or TRPV1, respectively. Analogs of known TRPA1 antagonists were screened for their TRPA1 inhibitory activity. Arbanol was identified as a novel TRPA1 inhibitor that can be used to reduce sensory irritation on the skin surface. TRP channels are crucial for sensory irritation on the skin surface.