title: Smad-interacting protein 1 affects acute and tonic, but not chronic pain.
abstract: BACKGROUND
  Smad-interacting protein 1 (also named Zeb2 and Zfhx1b) is a transcription factor that plays an important role in neuronal development and, when mutated, causes Mowat-Wilson syndrome (MWS). A corresponding mouse model carrying a heterozygous Zeb2 deletion was comprehensively analysed in the German Mouse Clinic. The most prominent phenotype was the reduced pain sensitivity. In this study, we investigated the role of Zeb2 in inflammatory and neuropathic pain.
  
  
  METHODS
  For this, we tested mutant Zeb2 animals in different models of inflammatory pain like abdominal constriction, formalin and carrageenan test. Furthermore, we studied the pain reactivity of the mice after peripheral nerve ligation. To examine the nociceptive transmission of primary sensory dorsal root ganglia (DRG) neurons, we determined the neuronal activity in the spinal dorsal horn after the formalin test using staining of c-Fos. Next, we characterized the neuronal cell population in the DRGs and in the sciatic nerve to study the effect of the Zeb2 mutation on peripheral nerve morphology.
  
  
  RESULTS
  The present data show that Zeb2 is involved in the development of primary sensory DRG neurons, especially of C- and Aδ fibres. These alterations contribute to a hypoalgesic phenotype in inflammatory but not in neuropathic pain in these Zeb2(+/-) mice.
  
  
  CONCLUSIONS
  Our data suggest that the under-reaction to pain observed in MWS patients results from a reduced responsivity to nociceptive stimulation rather than an inability to communicate discomfort.
authors.affiliation: Institute of Molecular Psychiatry, University of Bonn Medical Center, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Pradier
authors.forename: M
authors.initials: M
authors.lastname: Jeub
authors.forename: A
authors.initials: A
authors.lastname: Markert
authors.forename: D
authors.initials: D
authors.lastname: Mauer
authors.forename: K
authors.initials: K
authors.lastname: Tolksdorf
authors.forename: T
authors.initials: T
authors.lastname: Van de Putte
authors.forename: E
authors.initials: E
authors.lastname: Seuntjens
authors.forename: V
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: H
authors.initials: H
authors.lastname: Fuchs
authors.forename: M
authors.initials: M
authors.lastname: Hrabě de Angelis
authors.forename: D
authors.initials: D
authors.lastname: Huylebroeck
authors.forename: H
authors.initials: H
authors.lastname: Beck
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
authors.forename: I
authors.initials: I
authors.lastname: Rácz
mesh_terms: D059787:Acute Pain / Q000235:genetics*; D000818:Animals; D059350:Chronic Pain / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D019066:Facies; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006627:Hirschsprung Disease / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D051379:Mice; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009437:Neuralgia / Q000235:genetics* / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics*; D013116:Spinal Cord / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D018398:Homeodomain Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2