The [beta]3 subunit of the Na+,K+-ATPase mediates variable nociceptive sensitivity in the formalin test.
LaCroix-Fralish, Michael L. a; Mo, Gary b; Smith, Shad B. a; Sotocinal, Susana G. a; Ritchie, Jennifer a; Austin, Jean-Sebastien a; Melmed, Kara a; Schorscher-Petcu, Ara b; Laferriere, Audrey C. a; Lee, Tae Hoon a; Romanovsky, Dmitry c; Liao, Guochun d; Behlke, Mark A. e; Clark, David J. f; Peltz, Gary g; Seguela, Philippe b; Dobretsov, Maxim c; Mogil, Jeffrey S. a,*
144(3):294-302, August 2009.
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It is widely appreciated that there is significant inter-individual variability in pain sensitivity, yet only a handful of contributing genetic variants have been identified. Computational genetic mapping and quantitative trait locus analysis suggested that variation within the gene coding for the [beta]3 subunit of the Na ,K -ATPase pump (Atp1b3) contributes to inter-strain differences in the early phase formalin pain behavior. Significant strain differences in Atp1b3 gene expression, [beta]3 protein expression, and biophysical properties of the Na ,K pump in dorsal root ganglia neurons from resistant (A/J) and sensitive (C57BL/6J) mouse strains supported the genetic prediction. Furthermore, in vivo siRNA knockdown of the [beta]3 subunit produced strain-specific changes in the early phase pain response, completely rescuing the strain difference. These findings indicate that the [beta]3 subunit of the Na ,K -ATPase is a novel determinant of nociceptive sensitivity and further supports the notion that pain variability genes can have very selective effects on individual pain modalities.
(C) 2009 Lippincott Williams & Wilkins, Inc.