Methyl p‐hydroxybenzoate causes pain sensation through activation of TRPA1 channels

• Published in: British journal of pharmacology Vol. 151; no. 1; pp. 134 - 141
• Main Authors: Fujita, F, Moriyama, T, Higashi, T, Shima, A, Tominaga, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.05.2007; Nature Publishing; Nature Publishing Group
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - physiology; Cells, Cultured; Dose-Response Relationship, Drug; Humans; Male; Medical sciences; Membrane Proteins - drug effects; Membrane Proteins - physiology; methyl paraben; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - physiology; nociception; Pain - chemically induced; Parabens - pharmacology; Pharmacology. Drug treatments; Research Papers; Transient Receptor Potential Channels - drug effects; Transient Receptor Potential Channels - physiology; TRPA1; TRPA1 Cation Channel; Nociception; Sensation; Pain; TRPA1; methyl paraben
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707219

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 agonists of the transient receptor potential (TRP) A1 channels are known to have strong antibacterial activities. Therefore, a series of experiments was conducted to find out the effects of parabens on TRP channels expressed in sensory neurons, particularly the TRPA1 channels. 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 activated 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 channels 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 channels. British Journal of Pharmacology (2007) 151, 134–141. doi:10.1038/sj.bjp.0707219