title: The Yin and Yang of pain: variability in formalin test nociception and morphine analgesia produced by the Yin Yang 1 transcription factor gene.
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.
authors: Department of Psychology and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Canada.
authors: R E
authors: RE
authors: Sorge
authors: M L
authors: ML
authors: LaCroix-Fralish
authors: A H
authors: AH
authors: Tuttle
authors: A
authors: A
authors: Khoutorsky
authors: S G
authors: SG
authors: Sotocinal
authors: J-S
authors: JS
authors: Austin
authors: K
authors: K
authors: Melmed
authors: S
authors: S
authors: Labialle
authors: J V
authors: JV
authors: Schmidt
authors: J N
authors: JN
authors: Wood
authors: A K
authors: AK
authors: Naumova
authors: J S
authors: JS
authors: Mogil
mesh_terms: D000698:Analgesia; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D005557:Formaldehyde / Q000633:toxicity; D005727:Ganglia, Spinal / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000627:therapeutic use*; D009154:Mutation; D062559:NAV1.8 Voltage-Gated Sodium Channel / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D059225:Nociception; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D010641:Phenotype; D050986:YY1 Transcription Factor / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; D062559:NAV1.8 Voltage-Gated Sodium Channel; C568318:Scn10a protein, mouse; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D005557:Formaldehyde; D009020:Morphine