Inhibitory modulation of the pain sensor protein, TRPA1

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The transient receptor potential (TRP) channel subtype V1 (TRPV1) and A1 (TRPA1) are known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals. In this study, we investigated mechanisms of inhibitory modulation of these TRP channels. Following is the major findings of this study.1. We found that artemin or resveratrol can inhibit TRPA1. The mechanism is likely due to a decreasing of the channel density of TRPA1 on cell membranes. 2. Pinosylvin methyl ether can inhibit TRPV1 by changing the EC50, but not the maximum response of capsaicin-induced currents. 3. Etodolac can direct activate and subsequently desensitize TRPA1 through a covalent modification of cysteine residues. These data indicate that the inhibitory mechanism of modulation of TRP channels are various and complicated.