Methyl p-hydroxybenzoate causes pain sensation through activation of TRPA1 channels Fujita F, Moriyama T, Higashi T, Shima A, Tominaga M. Br J Pharmacol 151: 134-141, 2007.
Background and purpose: Parabens are commonly added in pharmaceutical, cosmetic and food products because of their wide antibacterial properties, low toxicity, inertness and chemical stability although the molecular mechanism of their antibacterial effect is not fully understood. Some of the TRPA1 agonists are known to have strong antibacterial activities. Therefore, a series of experiments was conducted to find out the effects of parabens on TRP channel expressed in sensory neurons including TRPA1.
Experimental approach: Effects of parabens, especially of methyl p-hydroxybenzoate (methyl paraben) on TRP channel activities were examined using Ca2+-imaging and patch-clamp methods. In addition, an involvement of methyl paraben in the development of pain-related behavior in mice was investigated.
Key results: Methyl paraben specifically activates TRPA1 in both HEK293 cells expressing TRPA1 and in mouse sensory neurons with an EC50 value of 4.4 mM, an attainable concentration in methyl paraben-containing products. Methyl paraben caused pain-related behavior in mice similar to that caused by allyl isothiocyanate, which was blocked by the TRP channel blocker ruthenium red.
Conclusions and implications: Our data indicate that methyl paraben is able to activate TRPA1 and can cause pain sensation. As such, methyl paraben provides a useful tool for investigating TRPA1 function and development of antinociceptive agents acting on TRPA1.