• Michael L LaCroix-Fralish, Gary Mo, Shad B Smith, Susana G Sotocinal, Jennifer Ritchie, Jean-Sebastien Austin, Kara Melmed, Ara Schorscher-Petcu, Audrey C Laferriere, Tae Hoon Lee, Dmitry Romanovsky, Guochun Liao, Mark A Behlke, David J Clark, Gary Peltz, Philippe Séguéla, Maxim Dobretsov, and Jeffrey S Mogil.
• Department of Psychology and Centre for Research on Pain, McGill University, 1205 Dr. Penfield Ave., Montreal, Que. H3A 1B1, Canada.
• Pain. 2009 Aug 1; 144 (3): 294-302.

AbstractIt 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 beta3 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, beta3 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 beta3 subunit produced strain-specific changes in the early phase pain response, completely rescuing the strain difference. These findings indicate that the beta3 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.

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