Formalin evokes calcium transients from the endoplasmatic reticulum

Michael J.M. Fischer, Kailey J. Soller, Susanne K. Sauer, Joanna Kalucka, Gianluigi Veglia, Peter W. Reeh

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


The formalin test is the most widely used behavioral screening test for analgesic compounds. The cellular mechanism of action of formaldehyde, inducing a typically biphasic pain-related behavior in rodents is addressed in this study. The chemoreceptor channel TRPA1 was suggested as primary transducer, but the high concentrations used in the formalin test elicit a similar response in TRPA1 wildtype and knockout animals. Here we show that formaldehyde evokes a dose-dependent calcium release from intracellular stores in mouse sensory neurons and primary keratinocytes as well as in non-neuronal cell lines, and independent of TRPA1. The source of calcium is the endoplasmatic reticulum and inhibition of the sarco/endoplasmic reticulum calcium-ATPase has a major contribution. This TRPA1-independent mechanism may underlie formaldehyde-induced pan-neuronal excitation and subsequent inflammation.

Original languageEnglish (US)
Article numbere0123762
JournalPloS one
Issue number4
StatePublished - Apr 15 2015

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© 2015 Fischer et al.


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