title: Variability in Capsaicin-stimulated Calcitonin Gene-related Peptide Release from Human Dental Pulp.
abstract: BACKGROUND
  The unique innervation and anatomic features of dental pulp contribute to the remarkable finding that any physical stimulation of pulpal tissue is painful. Furthermore, when pathological processes such as caries affect teeth and produce inflammation of the pulp, the pain experienced can be quite intense and debilitating. To better understand these underlying neurobiological mechanisms and identify novel analgesic targets for pulpally derived pain, we have developed a powerful ex vivo model using human tooth slices.
  
  
  METHODS
  Noncarious, freshly extracted teeth were collected and sectioned longitudinally into 1-mm-thick slices containing both dental pulp and the surrounding mineralized tissues. Tooth slices from 36 patients were exposed to 60 μmol/L capsaicin to stimulate the release of calcitonin gene-related peptide (CGRP) from nerve terminals in the pulp. Patient factors were analyzed for their effects on capsaicin-stimulated CGRP release using a mixed model analysis of variance.
  
  
  RESULTS
  Approximately one third of the variability observed in capsaicin-evoked CGRP release was attributable to differences between individuals. In terms of individual factors, there was no effect of anesthesia type, sex, or age on capsaicin-stimulated CGRP release. Using a within-subject study design, a significant effect of capsaicin on CGRP release was observed.
  
  
  CONCLUSIONS
  Capsaicin-stimulated CGRP release from dental pulp is highly variable between individuals. A within-subject study design improves the variability and maximizes the potential of this powerful translational model to test the efficacy of novel pharmacotherapeutic agents on human peripheral nociceptors.
authors.affiliation: Department of Endodontics, New York University College of Dentistry, New York, New York.
authors.forename: Lorel E
authors.initials: LE
authors.lastname: Burns
authors.affiliation: Department of Endodontics, New York University College of Dentistry, New York, New York.
authors.forename: Austin A
authors.initials: AA
authors.lastname: Ramsey
authors.affiliation: School of Dentistry, Department of Physiology, University of California San Francisco, San Francisco, California.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Emrick
authors.affiliation: Department of Epidemiology and Health Promotion, New York University College of Dentistry, New York, New York.
authors.forename: Malvin N
authors.initials: MN
authors.lastname: Janal
authors.affiliation: Department of Endodontics, New York University College of Dentistry, New York, New York. Electronic address: jlg15@nyu.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gibbs
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D003782:Dental Pulp / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008963:Molar; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000378:metabolism; D014082:Tooth Fractures; D055815:Young Adult
chemical_list: D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin
keywords: Calcitonin gene-related peptide; TRPV1; capsaicin; dental pulp; human tissue; pain; primary afferent; tooth slice; transient receptor potential cation channel V1; translational research