title: Capsaicin-sensitive Innervation Modulates the Development of Apical Periodontitis.
abstract: BACKGROUND
  Nociceptive neurons play a critical role in the detection of stimuli evoking actual or potential tissue injury. In addition, they are involved in neurogenic inflammation by the peripheral release of neuropeptides such as calcitonin gene-related peptide (CGRP). The dental pulp and periradicular tissues are innervated by capsaicin-sensitive neurons known to release CGRP. However, the role of these capsaicin-sensitive neurons in the development of apical periodontitis is largely unknown. The aim of this study was to evaluate the contribution of peptidergic neurons to the development of apical periodontitis.
  
  
  METHODS
  Neonatal Sprague-Dawley rats were injected with vehicle (control group) or a single subcutaneous capsaicin dose to cause the selective ablation of peptidergic neurons (neonatal capsaicin group). Ablation of capsaicin-sensitive neurons was verified with confocal microscopy, capsaicin-induced eye-wipe nocifensive behavior test, and by measurement of immunoreactive CGRP levels in the dental pulp. Five weeks after ablation, standardized pulp exposures were made in the mandibular left first molars. Mandibles were harvested at 7, 14, 21, and 28 days after pulp exposure and imaged with micro-computed tomography (μCT) to quantify apical lesion volume. Data were analyzed by using 2-way ANOVA analysis with Bonferroni post hoc test.
  
  
  RESULTS
  Rats in the control group displayed a robust capsaicin-induced nocifensive behavior, which was nearly abolished in the neonatal capsaicin group. In addition, the neonatal capsaicin group showed a significant depletion of susceptible neurons and CGRP in the dental pulp compared with control. Importantly, micro-computed tomography analysis showed larger periradicular lesions at 7 and 14 days after pulp exposure in the neonatal capsaicin group when compared with control.
  
  
  CONCLUSIONS
  Results identify a protective role for capsaicin-sensitive neurons in the initial phase of apical periodontitis. Thus, interventions or disorders that alter activity of capsaicin-sensitive fibers are likely to alter the development of apical periodontitis.
authors: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Department of Endodontics, Faculty of Dentistry, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Obadah N
authors: ON
authors: Austah
authors: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors: Nikita B
authors: NB
authors: Ruparel
authors: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors: Michael A
authors: MA
authors: Henry
authors: Department of Orthopedics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors: Roberto J
authors: RJ
authors: Fajardo
authors: Department of Orthopedics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors: James E
authors: JE
authors: Schmitz
authors: Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Electronic address: diogenes@uthscsa.edu.
authors: Anibal
authors: A
authors: Diogenes
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000009:adverse effects / Q000494:pharmacology*; D003782:Dental Pulp / Q000187:drug effects* / Q000294:innervation* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D020078:Neurogenic Inflammation / Q000378:metabolism / Q000473:pathology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010485:Periapical Periodontitis / Q000139:chemically induced* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin
keywords: Apical periodontitis; CGRP; TRPV1; endodontic infection; microCT; neurogenic inflammation; peptidergic nociceptors