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

Genes Brain Behav. 2013 Jun;12(4):405-13. doi: 10.1111/gbb.12030. Epub 2013 Mar 19.


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 Nav 1.8-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia*
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Cells, Cultured
  • Formaldehyde / toxicity
  • Ganglia, Spinal / cytology
  • Mice
  • Mice, Inbred C57BL
  • Morphine / therapeutic use*
  • Mutation
  • NAV1.8 Voltage-Gated Sodium Channel / genetics
  • NAV1.8 Voltage-Gated Sodium Channel / metabolism
  • Neurons / metabolism
  • Neurons / physiology
  • Nociception*
  • Pain / drug therapy
  • Pain / etiology
  • Pain / genetics*
  • Phenotype
  • YY1 Transcription Factor / genetics*


  • Analgesics, Opioid
  • NAV1.8 Voltage-Gated Sodium Channel
  • Scn10a protein, mouse
  • YY1 Transcription Factor
  • Yy1 protein, mouse
  • Formaldehyde
  • Morphine