title: Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities.
abstract: BACKGROUND
  Epidermal keratinocytes are increasingly recognized as active participants in the sensory transduction of itch and pain, processes known to involve primary afferent glutamatergic neurons. However the role of keratinocyte glutamate signaling in sensory functioning is not fully understood. Here, we present the observation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid type glutamate receptors (AMPAR) in epidermal keratinocytes.
  
  
  METHODS
  Immunohistochemical andin situhybridization analyses were conducted to assess the expression of AMPAR subunits in epidermal keratinocytes in mouse and human skin samples, and in organotypic cultures of human keratinocytes. In addition, RTPCR further confirmed the expression of GluA4-containing AMPAR in epidermal keratinocytes.
  
  
  RESULTS
  We found prominent immunolabeling (IL) for the GluA4 subunit of AMPAR in keratinocytes of glabrous and hairy skin of mouse epidermis, as well as in human epidermal keratinocytes. RTPCR confirmedGria4transcript expression in epidermal mouse keratinocytes. In addition, expression ofGRIA4mRNA was confirmed in epidermal human keratinocytes byin situhybridization. Immunohistochemical studies conducted in human skin biopsies from patients with atopic dermatitis (AD) and postherpetic neuralgia (PHN) demonstrate that keratinocyte expression of GluA4 can be altered under pathological conditions. Moreover, a decrease of GluA4 expression was observed in organotypic cultures of human keratinocytes after direct application of algogenic agents.
  
  
  CONCLUSIONS
  We provide evidence that GluA4-containing AMPAR are expressed in epidermal keratinocytes, that human pruritic and painful dermatopathologies have alterations in the keratinocyte expression levels of GluA4-containing AMPAR, and that itch and pain producing substances can directly regulate their production in keratinocytes.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, Washington University Pain Center, St Louis, MO, USA; Laboratory of Neuropharmacology, University Pompeu Fabra, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Cabañero
authors.affiliation: Department of Anesthesiology and Critical Care, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Irie
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, Washington University Pain Center, St Louis, MO, USA.
authors.forename: Marta
authors.initials: M
authors.lastname: Celorrio
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, Washington University Pain Center, St Louis, MO, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Trousdale
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, NY, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Owens
authors.affiliation: Transpharmation LTD, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Virley
authors.affiliation: Integrated Tissue Dynamics, Rensselaer, NY, USA.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Albrecht
authors.affiliation: Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
authors.affiliation: Integrated Tissue Dynamics, Rensselaer, NY, USA.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Rice
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, Washington University Pain Center, St Louis, MO, USA; Department of Neuroscience, Washington University School of Medicine, MO, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Morón