1. The Yin and Yang of pain: variability in formalin test nociception and morphine analgesia produced by the Yin Yang 1 transcription factor gene
- Author
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Kara Melmed, J. V. Schmidt, Jean-Sebastien Austin, Michael L. LaCroix-Fralish, Susana G. Sotocinal, John N. Wood, Jeffrey S. Mogil, Alexander H. Tuttle, Arkady Khoutorsky, Anna K. Naumova, Robert E. Sorge, and S. Labialle
- Subjects
Congenic ,Pharmacology ,Biology ,Behavioral Neuroscience ,Nociception ,medicine.anatomical_structure ,Neurology ,Opioid ,Dorsal root ganglion ,Genetics ,medicine ,Morphine ,μ-opioid receptor ,Transcription Factor Gene ,Transcription factor ,medicine.drug - 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 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.
- Published
- 2013
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