Jennifer L. Gibbs

Histological Findings of Revascularized/Revitalized Immature Permanent Molar with Apical Periodontitis Using Platelet-rich Plasma

INTRODUCTION An immature mandibular right first molar (#30) with apical periodontitis of a 9-year-old boy was treated with a revascularization/revitalization procedure using either a mixture of platelet-rich plasma (PRP) and a blood clot or a blood clot alone on the same tooth. METHODS Tooth #30 fractured 2 years and 1 month after the revascularization/revitalization procedure and could not be saved. The tooth was extracted and processed for histologic examination to determine the nature of the tissues that formed in the canals. RESULTS Clinically, the endodontic treatment of the case was successful based on the resolution of apical periodontitis and the absence of clinical signs and symptoms. Histologically, the tissues formed in the distal and mesial canals were mineralized tissue similar to cementoid/osteoid tissue and uninflamed fibrous connective tissue regardless of PRP or no PRP treatment. No pulp-like tissue characterized by the presence of odontoblast-like cells polarized along the dentin-like mineralized tissue was observed. CONCLUSIONS The tissues formed in the canals were mineralized tissue and some fibrous connective tissue. No pulp-like tissue characterized by the presence of odontoblast-like cells was observed lining the dentin-like mineralized tissue.

Public Health Surveillance of Dental Pain via Twitter

On Twitter, people answer the question, “What are you doing right now?” in no more than 140 characters. We investigated the content of Twitter posts meeting search criteria relating to dental pain. A set of 1000 tweets was randomly selected from 4859 tweets over 7 non-consecutive days. The content was coded using pre-established, non-mutually-exclusive categories, including the experience of dental pain, actions taken or contemplated in response to a toothache, impact on daily life, and advice sought from the Twitter community. After excluding ambiguous tweets, spam, and repeat users, we analyzed 772 tweets and calculated frequencies. Of the sample of 772 tweets, 83% (n = 640) were primarily categorized as a general statement of dental pain, 22% (n = 170) as an action taken or contemplated, and 15% (n = 112) as describing an impact on daily activities. Among the actions taken or contemplated, 44% (n = 74) reported seeing a dentist, 43% (n = 73) took an analgesic or antibiotic medication, and 14% (n = 24) actively sought advice from the Twitter community. Twitter users extensively share health information relating to dental pain, including actions taken to relieve pain and the impact of pain. This new medium may provide an opportunity for dental professionals to disseminate health information.

Histologic study of a human immature permanent premolar with chronic apical abscess after revascularization/revitalization.

INTRODUCTION Histologic studies of teeth from animal models of revascularization/revitalization are available; however, specimens from human studies are lacking. The nature of tissues formed in the canal of human revascularized/revitalized teeth was not well established. METHODS An immature mandibular premolar with infected necrotic pulp and a chronic apical abscess was treated with revascularization/revitalization procedures. At both the 18-month and 2-year follow-up visits, radiographic examination showed complete resolution of the periapical lesion, narrowing of the root apex without root lengthening, and minimal thickening of the canal walls. The revascularized/revitalized tooth was removed because of orthodontic treatment and processed for histologic examination. RESULTS The large canal space of revascularized/revitalized tooth was not empty and filled with fibrous connective tissue. The apical closure was caused by cementum deposition without dentin. Some cementum-like tissue was formed on the canal dentin walls. Inflammatory cells were observed in the coronal and middle third of revascularized/revitalized tissue. CONCLUSIONS In the present case, the tissue formed in the canal of a human revascularized/revitalized tooth was soft connective tissue similar to that in the periodontal ligament and cementum-like or bone-like hard tissue, which is comparable with the histology observed in the canals of teeth from animal models of revascularization/revitalization.

Radiographic and clinical outcomes of the treatment of immature permanent teeth by revascularization or apexification: a pilot retrospective cohort study.

INTRODUCTION This retrospective cohort study compared clinical and radiographic outcomes of endodontic treatment performed in immature nonvital permanent teeth by apexification (calcium hydroxide or apical barrier with mineral trioxide aggregate) versus revascularization. METHODS A comprehensive chart review was performed to obtain a cohort of previously completed cases with recalls. Clinical and radiographic data were collected for 31 treated teeth (19 revascularization and 12 apexification) with an average follow-up time of 17 months and a recall rate of 63%. Tooth survival, success rate, and adverse events were analyzed. Changes in radiographic root length, width, and area were quantified. RESULTS The majority of treated teeth survived throughout the study period, with 30 of 31 (97%) teeth surviving (18/19 [95%] revascularization and 12/12 apexification). Most cases were also clinically successful, with 27 of 31 (87%) meeting criteria for success (15/19 [78%] revascularization and 12/12 apexification; nonsignificant difference). A greater incidence of adverse events was observed in the revascularization group (8/19 [42%] vs 1/12 [11%] in apexification) (risk ratio = 5.1; P = .04; 95% confidence interval, 0.719-35.48). Although more revascularization cases than apexification cases showed an increase in radiographic root area and width, the effect was not statistically significant. CONCLUSIONS In this study, revascularization was not superior to other apexification techniques in either clinical or radiographic outcomes. Studies with large subject cohorts and long follow-up periods are needed to evaluate outcomes of revascularization and apexification while accounting for important covariants relevant to clinical success.

Nerve growth factor links oral cancer progression, pain, and cachexia.

Cancers often cause excruciating pain and rapid weight loss, severely reducing quality of life in cancer patients. Cancer-induced pain and cachexia are often studied and treated independently, although both symptoms are strongly linked with chronic inflammation and sustained production of proinflammatory cytokines. Because nerve growth factor (NGF) plays a cardinal role in inflammation and pain, and because it interacts with multiple proinflammatory cytokines, we hypothesized that NGF acts as a key endogenous molecule involved in the orchestration of cancer-related inflammation. NGF might be a molecule common to the mechanisms responsible for clinically distinctive cancer symptoms such as pain and cachexia as well as cancer progression. Here we reported that NGF was highly elevated in human oral squamous cell carcinoma tumors and cell cultures. Using two validated mouse cancer models, we further showed that NGF blockade decreased tumor proliferation, nociception, and weight loss by orchestrating proinflammatory cytokines and leptin production. NGF blockade also decreased expression levels of nociceptive receptors TRPV1, TRPA1, and PAR-2. Together, these results identified NGF as a common link among proliferation, pain, and cachexia in oral cancer. Anti-NGF could be an important mechanism-based therapy for oral cancer and its related symptoms. Mol Cancer Ther; 10(9); 1667–76. ©2011 AACR.

Histologic and Histobacteriologic Observations of Failed Revascularization/Revitalization Therapy: A Case Report

INTRODUCTION Mechanical debridement plays an important role in eliminating intracanal bacteria, such as biofilm on the canal walls and bacteria in the dentinal tubules. Mechanical debridement is not recommended for root canal disinfection in revascularization/revitalization therapy. Here we report a failed revascularization/revitalization case, which could be due to inadequate root canal disinfection without mechanical removal of biofilm and bacteria in dentinal tubules. METHODS A 6-year-old boy had a traumatic injury to tooth #9, which was avulsed and replanted within 40 minutes. The tooth subsequently developed a local swelling in the periapical area. The patient was referred to the Postgraduate Endodontic Clinic for revascularization/revitalization therapy on tooth #9. The treated tooth remained asymptomatic for 16 months and then developed pain and local periapical swelling. The oral surgeon extracted the revascularized/revitalized tooth. On request, the extracted tooth was processed for histologic and histobacteriologic examination. RESULTS The tissue in the canal was completely destroyed. Most bacteria were observed in the apical portion and not in the coronal portion of the canal and formed biofilm on the canal walls and penetrated into the dentinal tubules. CONCLUSIONS On the basis of histobacteriologic observations, the failure of revascularized/revitalized tooth could be due to inadequate root canal disinfection without mechanical debridement. It may be important to perform mechanical debridement as part of the revascularization/revitalization therapy to disrupt the biofilm on the canal walls and remove bacteria in the dentinal tubules because revascularization/revitalization therapy is able to increase thickening of the canal walls.

Attenuation of capsaicin-evoked mechanical allodynia by peripheral neuropeptide Y Y1 receptors

Abstract Neuropeptide Y (NPY) and its cognate receptors are important modulators of nociception and their expression is significantly altered following injury. In particular, previous studies have demonstrated that the Y1 subtype of NPY receptors inhibits nociceptive transmission from capsaicin‐sensitive terminals in the dorsal horn of the spinal cord. The present study evaluated the function of the Y1 receptor on peripheral terminals of primary afferent neurons by testing whether peripherally administered Y1 agonists and antagonists alter capsaicin‐evoked mechanical allodynia in rats and capsaicin‐evoked immunoreactive calcitonin gene‐related peptide (iCGRP) release from isolated superfused rat skin. Treatment with the Y1 agonist [Leu31,Pro34]‐NPY (0.5, 1, or 10 nmol) significantly inhibited capsaicin‐evoked mechanical allodynia in a dose‐dependent manner. This effect was reversible by pretreatment with the Y1 antagonist BIBO3304 (10 nmol). The anti‐allodynia produced by the Y1 agonist occurred at a peripheral site of action, because injection into the paw contralateral to the site of the capsaicin injection had no effect on paw withdrawal latencies. In isolated skin, application of [Leu31,Pro34]‐NPY (300 nM) significantly inhibited capsaicin‐evoked CGRP release. BIBO3304 reversed this inhibition, having itself no effect on capsaicin‐evoked iCGRP release. These studies indicate that the activation of peripheral Y1 receptors produces anti‐allodynia, possibly via the direct inhibition of capsaicin‐sensitive fibers.

Clinical and Radiographic Outcomes of Traumatized Immature Permanent Necrotic Teeth after Revascularization/Revitalization Therapy

INTRODUCTION Revascularization treatment is rapidly becoming an accepted treatment alternative for the management of endodontic pathology in immature permanent teeth with necrotic dental pulps. However, the success and timing of clinical resolution of symptoms, and radiographic outcomes of interest, such as continued hard tissue deposition within the root, are largely unknown. METHODS In this prospective cohort study, 20 teeth were treated with a standardized revascularization treatment protocol and monitored for clinical and radiographic changes for 1 year. Standardized radiographs were collected at regular intervals, and radiographic changes were quantified. RESULTS All 20 treated teeth survived during the 12-month follow-up period, and all 20 also met the clinical criteria for success at 12 months. As a group, the treated teeth showed a statistically significant increase in radiographic root width and length and a decrease in apical diameter, although the changes in many cases were quite small (such that the clinical significance is unclear). The within-case percent change in apical diameter after 3 months was 16% and had increased to 79% by 12 months, with 55% (11/20) showing complete apical closure. The within-case percent change in root length averaged less than 1% at 3 months and increased to 5% at 12 months. The within-case percent change in root thickness averaged 3% at 3 months and 21% at 12 months. CONCLUSIONS Although clinical success was highly predictable with this procedure, clinically meaningful radiographic root thickening and lengthening are less predictable after 1-year of follow-up. Apical closure is the most consistent radiographic finding.

Differential TRPV1 and TRPV2 Channel Expression in Dental Pulp

Hypersensitivity to thermal and mechanical stimuli can occur in painful pulpitis. To explore the neuro-anatomical basis of heat and mechanical sensitivity, we evaluated expression of TRPV1 (heat) and TRPV2 (heat/mechanical) channels in the cell bodies and terminal arborizations of neurons that innervate the dental pulp (DP) and periodontal tissues (PDL). We report that ~50% of trigeminal ganglion (TG) neurons retrogradely labeled from the DP express TRPV2, and this was significantly greater than the general expression of this channel in the TG (15%) and slightly more than what is expressed in the PDL by retrograde labeling (40%). The TRPV1 receptor, however, was less prevalent in neurons innervating the DP than their general expression in the TG (17% vs. 26%) and was more extensively expressed in neurons innervating the PDL (26%). Co-labeling studies showed that 70% of neurons that innervate the DP are myelinated. Approximately 1/3 of the retrogradely labeled neurons from the DP were calcitonin-gene-related-peptide-positive (peptide-expressing), but very few expressed the IB4 marker of non-peptidergic unmyelinated afferents. These findings suggest that the DP has a unique neurochemical innervation with regard to TRP receptor expression, which has significant implications for the mechanisms contributing to odontogenic pain and management strategies.

Neuropeptide Y inhibits capsaicin-sensitive nociceptors via a Y1-receptor-mediated mechanism.

Neuropeptide Y (NPY) is expressed in certain primary afferent fibers, is up-regulated in response to tissue injury and is capable of inhibiting nociceptive behavior at the spinal level. However, the spinal mechanism(s) for NPY-evoked antinociception is unknown. In this study, we evaluated the hypothesis that agonists at the NPY Y1 receptor subtype (Y1-R) inhibit exocytosis from the capsaicin-sensitive class of nociceptors. Using in vitro superfusion of rat dorsal spinal cord slices, pre-treatment with the Y1-R agonist [Leu(31)Pro(34)]NPY significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide with an EC(50) value of 10.6 nM. This inhibitory effect was concentration dependent, significantly attenuated by pre-treatment with the Y1 receptor antagonist BIBP3226 and reproduced by synthetic NPY. Examination of adult rat dorsal root ganglia using double immunofluorescent labeling revealed frequent co-localization of Y1 receptor immunoreactivity in vanilloid receptor type 1-immunoreactive neurons, indicating that Y1 agonists may directly modulate the capsaicin-sensitive class of nociceptors. Collectively, these results indicate that NPY is capable of inhibiting capsaicin-sensitive neurons via a Y1 receptor mechanism, suggesting the mechanisms for spinal NPY-induced antinociception is due, at least in part, to inhibition of central terminals of capsaicin-sensitive nociceptors.