title: Nav1.7 expression is increased in painful human dental pulp.
abstract: BACKGROUND
  Animal studies and a few human studies have shown a change in sodium channel (NaCh) expression after inflammatory lesions, and this change is implicated in the generation of pain states. We are using the extracted human tooth as a model system to study peripheral pain mechanisms and here examine the expression of the Nav1.7 NaCh isoform in normal and painful samples. Pulpal sections were labeled with antibodies against: 1) Nav1.7, N52 and PGP9.5, and 2) Nav1.7, caspr (a paranodal protein used to identify nodes of Ranvier), and myelin basic protein (MBP), and a z-series of optically-sectioned images were obtained with the confocal microscope. Nav1.7-immunofluorescence was quantified in N52/PGP9.5-identified nerve fibers with NIH ImageJ software, while Nav1.7 expression in myelinated fibers at caspr-identified nodal sites was evaluated and further characterized as either typical or atypical as based on caspr-relationships.
  
  
  RESULTS
  Results show a significant increase in nerve area with Nav1.7 expression within coronal and radicular fiber bundles and increased expression at typical and atypical caspr-identified nodal sites in painful samples. Painful samples also showed an augmentation of Nav1.7 within localized areas that lacked MBP, including those associated with atypical caspr-identified sites, thus identifying NaCh remodeling within demyelinating axons as the basis for a possible pulpal pain mechanism.
  
  
  CONCLUSIONS
  This study identifies the increased axonal expression and augmentation of Nav1.7 at intact and remodeling/demyelinating nodes within the painful human dental pulp where these changes may contribute to constant, increased evoked and spontaneous pain responses that characterize the pain associated with toothache.
authors.affiliation: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. luos@uthscsa.edu
authors.forename: Songjiang
authors.initials: S
authors.lastname: Luo
authors.forename: Griffin M
authors.initials: GM
authors.lastname: Perry
authors.forename: S Rock
authors.initials: SR
authors.lastname: Levinson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Henry
mesh_terms: D000328:Adult; D003782:Dental Pulp / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000378:metabolism; D062556:NAV1.7 Voltage-Gated Sodium Channel; D010146:Pain / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D004676:Myelin Basic Protein; D062556:NAV1.7 Voltage-Gated Sodium Channel; C486866:SCN9A protein, human; D015222:Sodium Channels