title: Unmyelinated nerve fibers in the human dental pulp express markers for myelinated fibers and show sodium channel accumulations.
abstract: BACKGROUND
  The dental pulp is a common source of pain and is used to study peripheral inflammatory pain mechanisms. Results show most fibers are unmyelinated, yet recent findings in experimental animals suggest many pulpal afferents originate from fibers that are myelinated at more proximal locations. Here we use the human dental pulp and confocal microscopy to examine the staining relationships of neurofilament heavy (NFH), a protein commonly expressed in myelinated afferents, with other markers to test the possibility that unmyelinated pulpal afferents originate from myelinated axons. Other staining relationships studied included myelin basic protein (MBP), protein gene product (PGP) 9.5 to identify all nerve fibers, tyrosine hydroxylase (TH) to identify sympathetic fibers, contactin-associated protein (caspr) to identify nodal sites, S-100 to identify Schwann cells and sodium channels (NaChs).
  
  
  RESULTS
  Results show NFH expression in most PGP9.5 fibers except those with TH and include the broad expression of NFH in axons lacking MBP. Fibers with NFH and MBP show NaCh clusters at nodal sites as expected, but surprisingly, NaCh accumulations are also seen in unmyelinated fibers with NFH, and in fibers with NFH that lack Schwann cell associations.
  
  
  CONCLUSIONS
  The expression of NFH in most axons suggests a myelinated origin for many pulpal afferents, while the presence of NaCh clusters in unmyelinated fibers suggests an inherent capacity for the unmyelinated segments of myelinated fibers to form NaCh accumulations. These findings have broad implications on the use of dental pulp to study pain mechanisms and suggest possible novel mechanisms responsible for NaCh cluster formation and neuronal excitability.
authors.affiliation: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. henrym2@uthscsa.edu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Henry
authors.forename: Songjiang
authors.initials: S
authors.lastname: Luo
authors.forename: S Rock
authors.initials: SR
authors.lastname: Levinson
mesh_terms: D058967:Contactin 1 / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology*; D006801:Humans; D018613:Microscopy, Confocal; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism*; D016900:Neurofilament Proteins / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C548669:CNTN1 protein, human; D058967:Contactin 1; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D009418:S100 Proteins; D015222:Sodium Channels; C482860:UCHL1 protein, human; C051774:neurofilament protein H; D014446:Tyrosine 3-Monooxygenase; D043222:Ubiquitin Thiolesterase