Activation of transient receptor potential ankyrin 1 by hydrogen peroxide

Hydrogen peroxide (H2O2), which is contained in industrial products, is also generated within cells. H2O2 causes pain but it has not been elucidated how it activates sensory neurons in the pain pathway. Here we show that transient receptor potential ankyrin 1 (TRPA1), expressed by sensory neurons in the pain pathway, is a receptor for H2O2. H2O2 activated mouse TRPA1 to induce Ca2+ influx and elicit non-selective cation currents. These effects of H2O2 were mimicked by both reactive oxygen species and reactive nitrogen species. Cysteine-reducing agents suppressed H2O2-induced TRPA1 activation, whereas cysteine-oxidizing agents activated TRPA1. H2O2 caused Ca2+ influx in a subset of dorsal root ganglia neurons, which responded to allyl isothiocyanate, a TRPA1 ligand. These results suggest that TRPA1 might be involved in the sensation of pain caused by H2O2.