title: Formalin evokes calcium transients from the endoplasmatic reticulum.
abstract: 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.
authors: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors: Michael J M
authors: MJ
authors: Fischer
authors: Department of Chemistry, University of Minnesota, Minneapolis, United States of America.
authors: Kailey J
authors: KJ
authors: Soller
authors: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors: Susanne K
authors: SK
authors: Sauer
authors: VIB Vesalius Research Center, Campus Gasthuisberg, KU Leuven, Leuven, Belgium.
authors: Joanna
authors: J
authors: Kalucka
authors: Department of Chemistry, University of Minnesota, Minneapolis, United States of America; Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, United States of America.
authors: Gianluigi
authors: G
authors: Veglia
authors: Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors: Peter W
authors: PW
authors: Reeh
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005557:Formaldehyde / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D018408:Patch-Clamp Techniques; D061251:Primary Cell Culture; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D005557:Formaldehyde; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium