A comparison of resin infiltration and microabrasion for postorthodontic white spot lesion.

INTRODUCTION: The objective of this research was to evaluate and compare the effectiveness of microabrasion and resin infiltration for white spot lesions (WSLs). METHODS: Patients with postorthodontic WSLs were enrolled and randomly assigned to the control, microabrasion, and resin-infiltration groups. Intraoral photographs were taken before and after (6 months later) treatment. WSL sizes were determined through ImageJ (Wayne Rasband, Kensington, Md). Integrated optical density (IOD) was determined for a WSL and its surrounding normal enamel through Image-Pro Plus (version 6.0; Media Cybernetics, Rockville, Md), and their differences of IOD were considered as the IOD surrogate for that WSL. The color change of WSL were measured through ΔE. RESULTS: A total of 27 eligible patients were enrolled; 9 subjects were assigned to each group, resulting in 56 teeth in the control group, 72 in the microabrasion group, and 58 in the resin-infiltration group. The ratios of WSL size (after/before) were similar between the microabrasion and resin-infiltration group (43.94 ± 0.03% vs 45.02 ± 0.03%; P = 0.96 > 0.05), but those of the 2 groups were significantly lower than those of the control group (92.15 ± 0.02%) (P <0.001). Moreover, the ratios of IOD (after/before) were significantly lower in the resin-infiltration group (22.94 ± 0.02%) than in the microabrasion (78.11 ± 0.03%) and control (83.79 ± 0.02%) (P <0.001) groups. The highest ΔE improvement was obtained by infiltration, but there was no significant difference between microabrasion and control group. CONCLUSIONS: Resin infiltration and microabrasion are comparably effective in reducing the sizes of WSL, but resin infiltration enjoys an esthetic advantage over microabrasion.

Nerve Growth Factor Enhances Tooth Mechanical Hyperalgesia Through C-C Chemokine Ligand 19 in Rats.

The nerve growth factor (NGF) plays an important role in the regulation of neuropathic pain. It has been demonstrated that calcitonin gene-related peptide (CGRP), a well-known contributor to neurogenic inflammation, increases neuroinflammatory pain induced by NGF. The inflammatory mediator that NGF most strongly induces is C-C chemokine ligand 19 (CCL19), which can recruit inflammatory cells by binding to the receptor CCR7 followed by promoting the response of neuroinflammation. However, the regulatory mechanism of NGF and CCL19 in tooth movement orofacial pain and the interaction between both are still unclear. In this study, male Sprague-Dawley rats were used to study the modulation of NGF on orofacial pain through CCL19 and the role of each in tooth movement pain in rats. The expression levels of CCL19 mRNA and protein were determined by real-time PCR and immunofluorescence, respectively. Pain levels were assessed by measuring the rats' bite force, which drops as pain rises. Meanwhile, by verifying the relationship between CGRP and CCL19, it was laterally confirmed that NGF could modulate tooth movement-induced mechanical hyperalgesia through CCL19. The results showed that the expression level of CCL19 rose with the increased NGF, and neurons expressing CGRP can express stronger CCL19. Compared with the baseline level, the bite force for all rats dropped sharply on day 1, reached its lowest level on day 3, and recovered gradually on day 5. All results indicated that NGF played an important role in tooth movement orofacial pain via positively regulating CCL19 expression in the trigeminal ganglia of rats. Additionally, CCL19 increased the sensitivity to experimental tooth movement orofacial pain. NGF can regulate CCL19 expression, although it may regulate other inflammatory pathways as well. This is the first report on the interactions and modulations of tooth movement orofacial pain by NGF through CCL19 in rats.

Retrograde nerve growth factor signaling modulates tooth mechanical hyperalgesia induced by orthodontic tooth movement via acid-sensing ion channel 3.

Orthodontic tooth movement elicits alveolar bone remodeling and orofacial pain that is manifested by tooth mechanical hyperalgesia. Nerve growth factor (NGF) is upregulated in periodontium and may modulate tooth mechanical hyperalgesia. The objectives were to examine the role of NGF in tooth mechanical hyperalgesia and to elucidate the underlying mechanisms. Tooth mechanical hyperalgesia was induced by ligating closed coil springs between incisors and molars in Sprague-Dawley rats. Retrograde labeling was performed by periodontal administration of fluor-conjugated NGF and the detection of fluorescence in trigeminal ganglia (TG). Lentivirus vectors carrying NGF shRNA were employed to knockdown the expression of NGF in TG. The administration of agonists, antagonists, and virus vectors into TG and periodontium was conducted. Tooth mechanical hyperalgesia was examined through the threshold of biting withdrawal. Our results revealed that tooth movement elicited tooth mechanical hyperalgesia that could be alleviated by NGF neutralizing antibody and that NGF was upregulated in periodontium (mainly in periodontal fibroblasts) and TG. Retrograde labeling revealed that periodontal NGF was retrogradely transported to TG after day 1. Acid-sensing ion channel 3 (ASIC3) and NGF were co-expressed in trigeminal neurons and the percentage of co-expression was significantly higher following tooth movement. The administration of NGF and NGF neutralizing antibody into TG could upregulate and downregulate the expression of ASIC3 in TG, respectively. NGF aggravated tooth mechanical hyperalgesia that could be alleviated by ASIC3 antagonist (APETx2). Moreover, NGF neutralizing antibody mitigated tooth mechanical hyperalgesia that could be recapitulated by ASIC3 agonist (GMQ). NGF-based gene therapy abolished tooth mechanical hyperalgesia and downregulated ASIC3 expression. Taken together, in response to force stimuli, periodontal fibroblasts upregulated the expressions of NGF that was retrogradely transported to TG, where NGF elicited tooth mechanical hyperalgesia through upregulating ASIC3. NGF-based gene therapy is a viable method in alleviating tooth-movement-induced mechanical hyperalgesia.

Comparison of pain perception, anxiety, and impacts on oral health-related quality of life between patients receiving clear aligners and fixed appliances during the initial stage of orthodontic treatment.

BACKGROUND AND OBJECTIVES: Clear aligner is an advanced orthodontic method with benefits of comfort, aesthetics, and convenience. This study aimed to compare pain perception, anxiety, and impacts on oral health-related quality of life (OHRQoL) between adult patients receiving clear aligners and fixed appliances during the initial stage of orthodontic treatments. MATERIAL AND METHODS: The two groups were well matched by ages, gender, and levels of malocclusion severity. Pain perception, anxiety, and OHRQoL were assessed through visual analogue scale, state-trait anxiety inventory, and oral health impact profile-14 (OHIP-14), respectively. And the comparison of above scores was performed by two-way analysis of variance. RESULTS: A total of 110 patients (55 pairs) were enrolled in this study. Orthodontic pain levels peaked on the first day and decreased gradually afterwards in both groups, which were significantly higher in the fixed group on the first, second, fourth, and fifth days. Likewise, anxiety levels peaked on the first day and decreased thereafter, with significant difference on the 1st, 3d, 5th, 7th, and 14th days. Moreover, the OHIP-14 scores increased and peaked on the first day and then gradually decreased for both groups, which were also significantly higher in the fixed group on the 1st, 7th, and 14th days. LIMITATIONS: More malocclusion types should be used for group matching. The effect of exclusion of small groups should be taken into consideration in sample size calculation. Income was significantly unbalanced between two groups due to higher cost of clear aligners, and random assignment of treatment modalities was unfeasible. CONCLUSIONS: Patients treated with clear aligners experienced lower pain levels, less anxiety, and higher OHRQoL as compared to those receiving fixed appliances.

Botulinum toxin A alleviates orofacial nociception induced by orthodontic tooth movement through nociceptin/orphanin-FQ pathway in rats.

OBJECTIVES: To investigate the effect and mechanism of botulinum neurotoxin type A (BoNT/A) in the modulation of orofacial nociception induced by orthodontic tooth movement in rats. METHODS: An orofacial nociception model was established in male Sprague-Dawley rats by ligating closed-coil springs between incisors and ipsilateral molars. There were two group sets of animals. For the first group set, 120 rats were randomly divided into four groups: no-force group (n = 30), force + saline group (n = 30), force + low dose BoNT/A group (1U/6 µL, n = 30), and force + high dose BoNT/A group (1U/6 µL, n = 30). BoNT/A and saline were injected into periodontal ligament to explore the nociceptive effect of BoNT/A. Ipsilateral trigeminal ganglia (TG) were harvested for detecting the expression levels of nociceptin/orphanin-FQ (N/OFQ). For the second group set, 36 rats were randomly divided into three force groups: BoNT/A + saline group (n = 12), BoNT/A + UFP-101 group (n = 12), and saline + UFP-101 group (n = 12). A potent N/OFQ receptor (NOP) antagonist (UFP-101) was used to examine the role of N/OFQ in BoNT/A-induced antinociception. Tooth-movement nociception level of all groups was evaluated by bite force and rat grimace scale (RGS) at baseline, day 1, day 3, day 5, day 7, day 14. RESULTS: The behavioral assessments showed the orofacial nociception level in the force + low dose BoNT/A group and force + high dose BoNT/A group were lower than that in the force + saline group. No significant difference was observed in orofacial nociception among no-force group, force + low dose and force + high dose group. The expression levels of N/OFQ in TG were elevated from day 1 and maintained a high level, presenting in descending order among the force + high dose, force + low dose, force + saline and no-force group, respectively. The nociception level of the BoNT/A + UFP-101 group was higher than that of the BoNT/A + saline group. No significant difference was observed between the BoNT/A + UFP-101 group and the saline + UFP-101 group. CONCLUSIONS: BoNT/A can exert an antinociceptive effect on orofacial nociception induced by tooth movement by stimulating the expression of N/OFQ in TG.

The dynamics of the oral microbiome and oral health among patients receiving clear aligner orthodontic treatment.

OBJECTIVES: This 6-month prospective clinical study assessed the impacts of Invisalign appliances on the oral bacterial community and oral health of patients. METHODS: Salivary samples were obtained from twenty-five adult patients receiving Invisalign aligner treatment before the treatment (Group B) and at a 6-month follow-up (Group P). The bacterial composition of each sample was determined using Illumina MiSeq sequencing of the bacterial 16S rRNA. Intra- and intergroup biodiversity was analyzed. Clinical periodontal parameters and daily oral hygiene habits were recorded. RESULTS: Reduction in plaque, increased daily brushing frequency, and decreased dessert intake were observed in Group P compared with that in Group B. A total of 1,853,952 valid reads were obtained from the 50 salivary samples, with 37,904 sequences per sample. No significant differences were detected in the intra- and intergroup biodiversity comparisons between the two groups. By clustering, 8,885 OTUs were identified and categorized into six major phyla: Firmicutes, Proteobacteria, Bacteroidetes, Fusobacteria, Actinobacteria, and Candidate_division_TM7_norank. At the genus level, compared with Group B, Group P demonstrated significantly increased Bacillus abundance and decreased Prevotella abundance. CONCLUSIONS: Our results suggested that the general biodiversity and salivary microbial community structure did not change significantly and that patients had increased beneficial oral hygiene habits and awareness during the first six months of Invisalign treatment. Hence, on the basis of this study, it appears that Invisalign aligner treatment did not induce deterioration of oral health nor significant biodiversity changes in oral bacterial communities, assuming that detailed oral hygiene instructions for both teeth and aligners were provided.

A novel technique of delivering viral vectors to trigeminal ganglia in rats.

The objective of this study was to develop a viable and reliable technique of delivering viral vectors to rat trigeminal ganglia. Adult Sprague-Dawley rats (200-300 g) were used, and lentiviral vectors containing enhanced green fluorescence protein and calcitonin gene-related peptide short hairpin RNA (shRNA) were generated. Following general anesthesia, viral vectors were delivered to rat trigeminal ganglia using the technique described in this study. Both X-ray and micro-computed tomography (micro-CT) were employed to verify the position of the needles when injecting the vectors. In vivo fluorescence imaging and immunostaining against enhanced green fluorescence protein were performed to determine the success of viral transduction.The levels of calcitonin gene-related peptide in trigeminal ganglia were determined using real-time PCR, and pain levels following injections were evaluated using the Rat Grimace Scale. Our results show that injection needles can be advanced precisely at the trigeminal fossa and that viral vectors can successfully transduce trigeminal ganglia. Moreover, the levels of calcitonin gene-related peptide at trigeminal ganglia were down-regulated on day 7 after viral transduction. Pain levels returned to baseline by day 7 following injection. Therefore, we suggest that our trigeminal ganglion-targeting technique could be used for delivering genes or drugs to rat trigeminal ganglia.

Effect of occlusal plane control procedure on hyoid bone position and pharyngeal airway of hyperdivergent skeletal Class II patients.

OBJECTIVE: To evaluate the effect of occlusal plane control on the hyoid bone position and pharyngeal airway of hyperdivergent skeletal Class II patients during orthodontic treatment. MATERIALS AND METHODS: Cephalograms of 47 hyperdivergent skeletal Class II subjects with occlusal plane control (OPC), and another 50 subjects without occlusal plane control (NOPC) were selected to compare the effects of the occlusal plane control procedure. Lateral cephalograms before treatment (T1), immediately after treatment (T2), and an average of 12 months after treatment (T3) were obtained, and 17 measurements were analyzed in each group and compared between groups. RESULTS: With respect to the T2-T1 changes, the sagittal discrepancies in both groups were alleviated. In the OPC group, both the occlusal and mandibular plane angles decreased, accompanied by anterior and superior movement and counterclockwise rotation of the hyoid bone. The overall changes from T3 to T1 in each group exhibited trends similar to that induced by treatment. As for pharyngeal airway space alterations, no significant difference in OPC group was presented throughout treatment or retention periods. CONCLUSIONS: The customized occlusal plane control procedure was effective for hyperdivergent skeletal Class II patients: The occlusal plane rotated counterclockwise, followed by a counterclockwise rotation of the mandibular plane. The hyoid bone moved anteriorly and superiorly, accompanied by its counterclockwise rotation. However, this procedure did not induce significant alteration of the pharyngeal airway space.

The effectiveness of the Herbst appliance for patients with Class II malocclusion: a meta-analysis.

OBJECTIVE: To systematically investigate review in literature the effects of the Herbst appliance for patients with Class II malocclusion patients. METHOD: We performed a comprehensive literature survey on PubMed, Web of Science, Embase, CENTRAL, SIGLE, and ClinicalTrial.gov up to December 2014. The selection criteria: randomized controlled trials or clinical controlled trials; using any kind of Herbst appliances to correct Class II division 1 malocclusions; skeletal and/or dental changes evaluated through lateral cephalograms. And the exclusion criteria: syndromic patients; individual case reports and series of cases; surgical interventions. Article screening, data extraction, assessment of risk of bias, and evaluation of evidence quality through GRADE were conducted independently by two well-trained orthodontic doctors. Consensus was made via group discussion of all authors when there is inconsistent information from the two. After that, sensitivity analysis and subgroup analysis were performed to evaluate the robustness of the meta-analysis. RESULTS: Twelve clinical controlled trials meet the above-mentioned criteria, and were included in this analysis. All included studies have eleven measures taken during both active treatment effect and long term effect periods, including four angular ones (i.e., SNA, SNB, ANB, mandibular plane angle) and seven linear ones (i.e. Co-Go, Co-Gn, overjet, overbite, molar relationship, A point-OLp, Pg-OLp) during active treatment effect period were statistically pooled. Meta-analysis and sensitivity analysis demonstrated that all these measures showed consistent results except for SNA, ANB, and overbite. Subgroup analysis showed significant changes in SNA, overbite, and Pg-OLp. Publication bias was detected in SNB, mandibular plane angle, and A point-OLp. CONCLUSION: The Herbst appliance is effective for patients with Class II malocclusion in active treatment period. Especially, there are obvious changes on dental discrepancy and skeletal changes on Co-Gn. As to its long-term effects, more evidence is needed to draw conclusions.

The role of periodontal ASIC3 in orofacial pain induced by experimental tooth movement in rats.

OBJECTIVES: This study aimed to clarify the roles of Acid-sensing ion channel 3 (ASIC3) in orofacial pain following experimental tooth movement. MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into the experimental group (40g, n = 30) and the sham group (0g, n = 30). Closed coil springs were ligated between maxillary incisor and molars to achieve experimental tooth movement. Rat grimace scale (RGS) scores were assessed at 0, 1, 3, 5, 7, and 14 days after the placement of the springs. ASIC3 immunostaining was performed and the expression levels of ASIC3 were measured through integrated optical density/area in Image-Pro Plus 6.0. Moreover, 18 rats were divided into APETx2 group (n = 6), amiloride group (n = 6), and vehicle group (n = 6), and RGS scores were obtained compared among them to verify the roles of ASIC3 in orofacial pain following tooth movement. RESULTS: ASIC3 expression levels became significantly higher in the experimental group than in sham group on 1, 3, and 5 days and became similar on 7 and 14 days. Pain levels (RGS scores) increased in both groups and were significantly higher in the experimental group on 1, 3, 5, and 7 days and were similar on 14 days. Periodontal ASIC3 expression levels were correlated with orofacial pain levels following experimental tooth movement. Periodontal administrations of ASIC3 antagonists (APETx2 and amiloride) could alleviate pain. LIMITATION: This study needs to be better evidenced by RNA interference of ASIC3 in periodontal tissues in rats following experimental tooth movement. Moreover, we hope further studies would concentrate on the pain perception of ASIC3 knockout (ASIC3-/-) mice. CONCLUSIONS: Our results suggest that periodontal ASIC3 plays an important role in orofacial pain induced by experimental tooth movement.

The effectiveness of oral appliances for obstructive sleep apnea syndrome: A meta-analysis.

OBJECTIVE: To evaluate the effectiveness of oral appliances (OAs) for managing patients with obstructive sleep apnea (OSA). METHODS: PubMed, Embase, Web of Science, CENTRAL and SIGLE were electronically searched from January 1980 to September 2015 for randomized or nonrandomized controlled trials that assessed the effectiveness of OAs on OSAS. The processes of study search, selection, data extraction, assessment of risk of bias and evaluation of evidence quality were conducted independently by two reviewer authors. Meta-analyses were performed in Review Manager 5, Stata11.0 and StatsDirect 2.7.9. RESULTS: Finally, we included 17 eligible studies which compared OAs and placebo or blank control. Six outcomes were assessed in this meta-analysis, i.e., apnea hypopnea index (AHI), respiratory arousal index (RAI), minimum oxygen saturation(MinSaO2), rapid eye movement (REM) sleep, sleep efficiency and Epworth Sleepiness Scale (ESS). Meta-analysis revealed that the pooled mean differences were -10.26 [95% CI: (-12.59, -7.93)], -9.03 [95% CI: (-11.89, -6.17)], 3.08 [95% CI: (1.97, 4.19)], 0.36 [95% CI: (-0.30, 1.02)], 1.34 [95% CI: (-0.05, 2.73)] and -1.76 [95% CI: (-2.57, -0.94)], respectively. The sensitivity analysis and subgroup analysis displayed generally robust results except for MinSaO2, REM sleep and sleep efficiency. Furthermore, publication bias was detected in RAI and MinSaO2. CONCLUSIONS: The available evidence indicates benefits in respiration and sleep quality with oral appliances as compared to placebo devices or blank control, while we cannot determine its effectiveness in sleep efficiency and sleep architecture alterations. However, due to low evidence quality as revealed by GRADE, this finding should be interpreted with caution. CLINICAL SIGNIFICANCE: Through critical meta-analyses, we found that oral appliances are effective in respiration improving and sleep quality. The existing evidence supports the employment of OAs as a recommendable treatment option for OSA. This meta-analysis helps to direct clinical practice and future research, and promises to be of great interest for both practitioners and researchers.

Periodontal CGRP contributes to orofacial pain following experimental tooth movement in rats.

Calcitonin-related gene peptide (CGRP) plays an important role in orofacial inflammatory pain. The aim of this study was to determine whether periodontal CGRP contributes to orofacial pain induced by experimental tooth movement in rats. Male Sprague-Dawley rats were used in this study. Closed coil springs were used to deliver forces. Rats were euthanized on 0d, 1d, 3d, 5d, 7d, and 14d following experimental tooth movement. Then, alveolar bones were obtained for immunostaining of periodontal tissues against CGRP. Two hours prior to euthanasia on each day, orofacial pain levels were assessed through rat grimace scale. CGRP and olcegepant (CGRP receptor antagonist) were injected into periodontal tissues to verify the roles of periodontal CGRP in orofacial pain induced by experimental tooth movement. Periodontal CGRP expression levels and orofacial pain levels were elevated on 1d, 3d, 5d, and 7d following experimental tooth movement. The two indices were significantly correlated with each other and fitted into a dose-response model. Periodontal administration of CGRP could elevate periodontal CGRP expressions and exacerbate orofacial pain. Moreover, olcegepant administration could decrease periodontal CGRP expressions and alleviate orofacial pain. Therefore, periodontal CGRP plays an important role in pain transmission and modulation following experimental tooth movement. We suggest that it may participate in a positive feedback aiming to amplify orofacial pain signals.