The Yin and Yang of pain: Variability in formalin test nociception and morphine analgesia produced by the Yin Yang 1 transcription factor gene

Academic Article

Abstract

  • We recently observed a reliable phenotypic difference in the inflammatory pain sensitivity of a congenic mouse strain compared to its background strain. By constructing and testing subcongenic strains combined with gene-expression assays, we provide evidence for the candidacy of the Yy1 gene - encoding the ubiquitously expressed and multifunctional Yin Yang 1 transcription factor - as responsible. To confirm this hypothesis, we used a Cre/lox strategy to produce mutant mice in which Yy1 expression was ablated in Nav1.8-positive neurons of the dorsal root ganglion. These mutants also displayed reduced inflammatory pain sensitivity on the formalin test. Further testing of pain-related phenotypes in these mutants revealed robustly increased sensitivity to systemic and spinal (but not supraspinal) morphine analgesia, and greatly increased endogenous (swim stress-induced) opioid analgesia. None of the known biological roles of Yin Yang 1 were suggestive of such a phenotype, and thus a novel player in pain modulatory systems has been identified. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.
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    Author List

  • Sorge RE; Lacroix-Fralish ML; Tuttle AH; Khoutorsky A; Sotocinal SG; Austin JS; Melmed K; Labialle S; Schmidt JV; Wood JN
  • Start Page

  • 405
  • End Page

  • 413
  • Volume

  • 12
  • Issue

  • 4