The β 3 subunit of the Na +,K +-ATPase mediates variable nociceptive sensitivity in the formalin test

• Published in: Pain (Amsterdam) Vol. 144; no. 3; pp. 294 - 302
• Main Authors: LaCroix-Fralish, Michael L., Mo, Gary, Smith, Shad B., Sotocinal, Susana G., Ritchie, Jennifer, Austin, Jean-Sebastien, Melmed, Kara, Schorscher-Petcu, Ara, Laferriere, Audrey C., Lee, Tae Hoon, Romanovsky, Dmitry, Liao, Guochun, Behlke, Mark A., Clark, David J., Peltz, Gary, Séguéla, Philippe, Dobretsov, Maxim, Mogil, Jeffrey S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 2009
• Subjects: Formalin; Gene mapping; Genetics; Nociception; Sodium–potassium pump; Nociception; Sodium–potassium pump; Formalin; Genetics; Gene mapping
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2009.04.028

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 β 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, β 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 β 3 subunit produced strain-specific changes in the early phase pain response, completely rescuing the strain difference. These findings indicate that the β 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.