Formalin evokes calcium transients from the endoplasmatic reticulum

• Published in: PloS one 2015-04, Vol.10 (4), p.e0123762
• Main Authors: Fischer, Michael J M, Soller, Kailey J, Sauer, Susanne K, Kalucka, Joanna, Veglia, Gianluigi, Reeh, Peter W
• Format: Article
• Language: English
• Subjects: Analgesics; Animals; ATPases; Behavior; Biochemistry; Ca2+-transporting ATPase; Calcium; Calcium (intracellular); Calcium (reticular); Calcium - metabolism; Calcium Signaling; Cell lines; Diabetic neuropathy; Endoplasmic reticulum; Endoplasmic Reticulum - drug effects; Endoplasmic Reticulum - metabolism; Formaldehyde; Formaldehyde - pharmacology; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Gene Expression Regulation; HEK293 Cells; Humans; Keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Laboratory animals; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice; Mice, Inbred C57BL; Neurons; Pain; Pain - chemically induced; Pain - genetics; Pain - metabolism; Pain - physiopathology; Pain Measurement; Pain perception; Patch-Clamp Techniques; Physiology; Primary Cell Culture; Rabbits; Rats; Rats, Wistar; Rodents; Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism; Sensory neurons; Sensory Receptor Cells - cytology; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - metabolism; Transient Receptor Potential Channels - genetics; Transient Receptor Potential Channels - metabolism; TRPA1 Cation Channel
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0123762

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.