Direct effect of endodontic sealers on trigeminal neuronal activity.
BACKGROUND
Endodontic sealers are selected on the basis of their antimicrobial properties and ability to provide a tight seal. Sealer extrusions, whether intentional or unintentional, are common during obturation procedures. Such events have been correlated with increased postoperative discomfort and persistent pain states. However, the mechanisms underlying this phenomenon are largely unknown. Thus, we sought to evaluate the effect of commonly used endodontic sealers on peripheral nociceptors. We hypothesized that endodontic sealers can directly activate trigeminal nociceptors in a concentration-dependent manner, resulting in release of calcitonin gene-related peptide (CGRP), a potent modulator of neurogenic inflammation.


METHODS
Rat trigeminal sensory neurons were exposed in vitro to vehicle, zinc oxide-eugenol (ZOE)-based sealer, AH Plus, EndoSequence BC sealer, or RealSeal SE. Neuronal activation was measured by quantification of neuropeptide (CGRP) release. In addition, cultured neurons were also subjected to the set form of all 4 sealers. The concentration of CGRP released was quantified by using a radioimmunoassay. Data were analyzed by using one-way analysis of variance with Newman-Keuls multiple comparison post hoc test.


RESULTS
Both ZOE-based sealer and AH Plus in their fresh form evoked greater CGRP release than the control groups. Conversely, EndoSequence BC and RealSeal sealers both reduced basal GCRP release at all concentrations tested. Evaluation of the set sealers revealed that only ZOE-based sealer evoked significant CGRP release compared with its control group.


CONCLUSIONS
Overall, our results suggest that sealers can directly activate trigeminal nociceptors, leading to a robust release of CGRP, and may therefore lead to pain and neurogenic inflammation. This direct activation along with the immunologic response may underlie the symptoms and flare-up occurrences often seen with sealer extrusions.
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Nikita B
NB
Ruparel
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Shivani B
SB
Ruparel
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Paul B
PB
Chen
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Blake
B
Ishikawa
Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Electronic address: Diogenes@uthscsa.edu.
Anibal
A
Diogenes
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000378:metabolism; D002130:Calcium Phosphates / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003188:Composite Resins / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004853:Epoxy Resins / Q000494:pharmacology; D008297:Male; D020078:Neurogenic Inflammation / Q000139:chemically induced; D009619:Nociceptors / Q000187:drug effects*; D010087:Oxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012387:Root Canal Filling Materials / Q000494:pharmacology*; D017640:Silicates / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000187:drug effects; D014276:Trigeminal Nerve / Q000187:drug effects*; D015035:Zinc Oxide-Eugenol Cement / Q000494:pharmacology
D002130:Calcium Phosphates; D003188:Composite Resins; D004338:Drug Combinations; C550603:EndoSequence root repair material; D004853:Epoxy Resins; D010087:Oxides; C511498:Real Seal composite resin; D012387:Root Canal Filling Materials; D017640:Silicates; D015035:Zinc Oxide-Eugenol Cement; C534916:epoxy resin-based root canal sealer; D015740:Calcitonin Gene-Related Peptide
AH Plus; CGRP; EndoSequence BC sealer; RealSeal SE; endodontic sealer; neuropeptide; neuroscience; obturation; pain; trigeminal neurons; zinc oxide eugenol