Search

BACKGROUND Orthodontic treatment is the main treatment approach for malocclusion. Orthodontic pain is an inevitable undesirable adverse reaction during orthodontic treatment. It is reported orthodontic pain has become one of the most common reason that patients withdraw from orthodontic treatment. Therefore, understanding the underlying mechanism and finding treatment of orthodontic pain are in urgent need. AIMS This article aims to sort out the mechanisms and treatments of orthodontic pain, hoping to provide some ideas for future orthodontic pain relief. MATERIALS Tooth movement will cause local inflammation. Certain inflammatory factors and cytokines stimulating the trigeminal nerve and further generating pain perception, as well as drugs and molecular targeted therapy blocking nerve conduction pathways, will be reviewed in this article. METHOD We review and summaries current studies related to molecular mechanisms and treatment approaches in orthodontic pain control. RESULTS Orthodontics pain related influencing factors and molecular mechanisms has been introduced. Commonly used clinical methods in orthodontic pain control has been evaluated. DISCUSSION With the clarification of more molecular mechanisms, the direction of orthodontic pain treatment will shift to targeted drugs.

Periosteum is expected for bone repairing due to excellent regenerative potential. PDCs are the main source of cells for promoting bone repair. However, PDCs from different sites have been confirmed to be site specific due to their distinct embryonic origin and the methods of bone formation. Hippo-YAP pathway is proved to play a critical role in fate decision of mesenchymal stem cells. The effect of Hippo-YAP on PDCs has not been reported so far. Hence, we aim to explore the differences of PDCs from mandible and femur along with their possible responses to YAP signaling. mPDCs and fPDCs were obtained and tested through flow cytometry for identification. Follow-up results illustrated mPDCs was cubic shape and with better proliferation while fPDCs preferred slender cell shape with worse cell viability compared with mPDCs. mPDCs was superior to fPDCs in ALP activity, related mRNA expression and calcium deposits in late stage. Interestingly, downregulation of YAP promoted the ALP activity, related mRNA expression and calcium deposits of fPDCs while hindered that of mPDCs in vitro. Moreover, implant animal model in mandible and femur were constructed for evaluation in vivo. Histological results were similar to the results in vitro. We speculate this may result from their different embryonic origin and the way of bone formation. Taken together, results available suggested that mPDCs may serve as more optimal seed cells for tissue engineering compared with fPDCs; however, considering their different response to YAP signaling, to ensure sufficient YAP expression in mPDCs and appropriate declining YAP expression in fPDCs may establish better osteogenesis.

Additional file 3: Figure S1. Full results of Western blot analysis for the quantification of N/OFQ expression in trigeminal ganglia. Figure S2. Full results of Western blot analysis of CGRP expression in trigeminal ganglion of rats in NS group, N/OFQ group and UFP-101 group. Figure S3. Full results of Western blot analysis of N/OFQ expression in trigeminal ganglion of rats in NS group, control lentivirus group and PNOC lentivirus group.

Additional file 1: Table S1. Grouping of experimental animals.

Additional file 2: Rat PNOC overexpression sequence. The specific sequences were retrieved from GenBank (NM_013007), with red indicating PNOC mRNA sequence, and ACCGGT is AgeI enzyme cutting site.

Additional file 2: Figure S1. Infiltrating immunocytes differences. (A) The volcano-plot demonstrates the fold changes of 22 immunocytes in chronic periodontitis compared with aggressive. (B) Compositional differences of 22 immunocytes between chronic and aggressive periodontitis presented by violin-plot (blue means aggressive and red means chronic). (C) The volcano-plot demonstrates the fold changes of 22 immunocytes in male periodontitis compared with female. (D) Compositional differences of 22 immunocytes between male and female periodontitis presented by violin-plot (blue means male and red means female). (E) Correlations between infiltrating immunocyte fractions and patient ages were presented by bar-plot. (F-G) The two significantly age-related immunocytes were presented by scatter plot. Figure S2.(A) Least absolute shrinkage and selection operator (LASSO) coefficient profiles of 22 immunocytes fractions. The dotted line indicates the value chosen by ten-fold cross-validation. (B) Ten-fold cross-validation for tuning parameter selection in the LASSO regression. The partial likelihood deviance is plotted against log (λ), where λ is the tuning parameter. Partial likelihood deviance values are shown, with error bars representing SE. The dotted vertical lines are drawn at the optimal values by minimum criteria and 1-SE criteria. Figure S3. Supplementary information for immune subtype analysis. (A) Estimation of the rank: Quality measures computed from 200 runs for each value of r. (B) Estimation of the rank: Consensus matrices computed from 10 runs for each value of r. (C-D) Heatmap of the mixture coefficient and the basis matrices for all immune genes. Figure S4. Supplementary information for WGCNA analysis. (A) analysis of the scale-free ft index for various soft-thresholding powers beta. (B) Analysis of the mean connectivity for various soft-thresholding powers. (C) The protein-protein interaction network of hub genes in turquoise module. (D) The top ten positive and negative plasma cell fraction related genes, calculated by pearson correlation analysis.

Data sources The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase. Randomised controlled trials (RCTs) of orthodontic treatment to correct prominent lower front teeth were included. Study screening, risk of bias assessment and data extraction were carried out independently by two reviewers. The mean differences with 95% confidence intervals were calculated for continuous data. Meta-analysis was undertaken when studies of similar comparisons reported comparable outcome measures. A fixed-effect model was used. The l2 statistic was used as a measure of statistical heterogeneity. Seven RCTs (339 patients) were included in this review. One study was assessed as at low risk of bias, three at high risk of bias and three at unclear risk. Four studies reported on the use of a facemask, two on the chin cup, one on the tandem traction bow appliance and one on mandibular headgear. One study reported on both the chin cup and mandibular headgear appliances. One study (n = 73, low quality evidence), comparing a facemask to no treatment, reported a mean difference (MD) in overjet of 4.10 mm (95% confidence interval (CI) 3.04 to 5.16; P value < 0.0001) favouring the facemask treatment. Three studies (n = 155, low quality evidence) reported ANB differences immediately after treatment with a facemask when compared to an untreated control. The pooled data showed a statistically significant MD in ANB in favour of the facemask of 3.93° (95% CI 3.46 to 4.39; P value < 0.0001). There was significant heterogeneity between these studies (I2 = 82%). This is likely to have been caused by the different populations studied and the different ages at the time of treatment. One study (n = 73, low quality evidence) reported outcomes of the use of the facemask compared to an untreated control at three years follow-up. This study showed that improvements in overjet and ANB were still present three years post-treatment. In this study, adverse effects were reported, but due to the low prevalence of temporomandibular (TMJ) signs and symptoms no analysis was undertaken. Two studies (n = 90, low quality evidence) compared the chin cup with an untreated control. Both studies found a statistically significant improvement in ANB, and one study also found an improvement in the Wits appraisal. Data from these two studies were not suitable for pooling. A single study of the tandem traction bow appliance compared to untreated control (n = 30, very low quality evidence) showed a statistically significant difference in both overjet and ANB favouring the intervention group. The remaining two studies did not report the primary outcome of this review. There is some evidence that the use of a facemask to correct prominent lower front teeth in children is effective when compared to no treatment on a short-term basis. However, in view of the general poor quality of the included studies, these results should be viewed with caution. Further randomised controlled trials with long follow-up are required.