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This study aimed to evaluate the analgesic effects of low-level laser therapy (LLLT) and paracetamol-caffeine in controlling orthodontic pain induced during different stages of leveling and alignment orthodontic treatment. Fifty-four patients with mild to moderate crowded arches were enrolled. Elastomeric separators were placed, followed by fixed appliance bonding one week later. Archwires were replaced according to a predefined sequence until reaching the final 0.019 × 0.025-inch stainless steel wires. The first group received a beam of GaAlAs-Laser before separator placement or any archwire replacement, whereas the second group received paracetamol-caffeine tablets (the drug). Patients in the control group did not receive any procedure. A numeric rating scale (NRS) was used to assess spontaneous and chewing pain immediately, after 1, 24, 48 h, one week, and on the next visit of any replacement. The pain perception reached its peak after 24 h of any replacement. The intensity of pain after 24 and 48 h of separators’ placement and initial archwires’ engagement was significantly greater than pain induced by 0.016, 0.016 × 0.022, 0.017 × 0.025, and 0.019 × 0.025 NiTi and 0.019 × 0.025 SS archwires in all groups for spontaneous and chewing pain scores. Pain scores in the LLLT group were significantly smaller than those of the control group after 48 h of separation and after 24 and 48 h of rectangular archwire insertion. No significant differences were observed between the drug and control groups. The highest pain levels were induced during the initial stages (separation and initial archwire) of orthodontic treatment. LLLT was able to reduce the peak of high-level pain just during separation and was not highly effective throughout the treatment course. On the other hand, the paracetamol-caffeine combination was not very effective in reducing pain perception throughout the treatment course. This trial was registered at Clinical Trials.gov (Identifier NCT03400111), registered on 17/01/2018.

This study investigated the use of salivary and serum chromogranin A (CgA) as biomarkers of acute stress and pain perception during the initial phase of fixed orthodontic treatment. Twenty-five patients aged 15–25 years, scheduled for non-extraction therapy with fixed appliances, were enrolled, and unstimulated saliva as well as venous blood samples were collected at baseline, 24 h, 72 h, and one month after appliance placement. Pain levels were measured using a 10-cm visual analogue scale (VAS). Both salivary and serum CgA levels showed a significant rise at 24 h compared to baseline, followed by a gradual return towards baseline by one month. Pain intensity peaked at 24 h (mean 8.07 ± 1.18) and decreased at 72 h and one month, with female participants reporting higher pain scores than males at 24 h. No significant gender differences were observed in CgA levels. The similar patterns of biomarker increase and self-reported pain indicate that CgA reflects the short-term stress response linked to appliance placement. Monitoring salivary CgA could thus offer clinicians a non-invasive method to predict discomfort, facilitate early interventions, and help patients adapt to orthodontic treatment.

Background To explore the effect and mechanism of hippocampus on experimental orthodontic pain-induced anxiety. Methods Herein, we document a novel modeling method whereby the nickel–titanium (Ni–Ti) orthodontic wire was fixed stably in the oral cavity of mice with a ligation technique to induce stable distal movement of maxillary incisors to mimic orthodontic tooth movement. At the experimental endpoint, serum corticosterone assay, Golgi staining and Micro-CT were performed in each group after oral-facial mechanical pain sensitivity assessment and open field test. Results The mechanical pain sensitivity of experimental tooth movement pain (ETMP) mice had an apparent increased elicited following tooth movement. And anxiety-like behavior was developed: reduced the time proportion of center zone and the total moving distance in the open field test and the elevated serum corticosterone levels in ETMP mice relative to control group mice. The Golgi staining in ventral hippocampal CA1 revealed that neural spine density, dendritic length and number of dendrites are reduced markedly in ETMP mice compared with the control group. Conclusion Experimental orthodontic pain drives emotional anxiety through the plasticity changes in decreased neuronal complexity and reduced spine density in ventral hippocampal CA1 in mice.

Objectives The objective of this systematic review and meta-analysis was to evaluate the effect of chewing gum on orthodontic pain and to determine the rate of bracket breakage associated with fixed orthodontic appliances. Methods This review and its reporting were performed according to the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Six electronic databases were searched up to March 16, 2023, to identify relevant studies that met the inclusion and exclusion criteria. Furthermore, grey literature resources were searched. The Cochrane Collaboration Risk of Bias tool 2 was used to assess the quality of the included studies. Meta-analysis was conducted using RevMan, and sensitivity analysis and publication bias analysis were performed using STATA software. GRADE tool was used to evaluate the certainty of evidence. Results Fifteen studies with 2116 participants were ultimately included in this review, and 14 studies were included in the meta-analysis. Compared with the blank group, chewing gum had a significant pain relieving effect at all times after fixation of the initial archwire ( P  ≤ 0.05). No significant difference was found between the chewing gum group and the analgesics group at any timepoints ( P  > 0.05). Only four studies evaluated the rate of bracket breakage and revealed that chewing gum did not increase the rate of bracket breakage. The sensitivity analysis showed that there was no significant difference in the pooled outcomes after the included studies were removed one at times, and Egger analysis revealed no significant publication bias in included studies ( P  > 0.05). Conclusions Chewing gum is a non-invasive, low-cost and convenient method that has a significant effect on relieving orthodontic pain and has no effect on the rate of bracket breakage. Therefore, chewing gum can be recommended as a suitable substitute for analgesics to reduce orthodontic pain.

Background The objective of this randomized clinical trial was to evaluate Low-Level Laser Therapy (LLLT) effectiveness in spontaneous and chewing pain reduction following initial orthodontic archwire placement. Methods 26 patients (mean age 20.07 ± 3.13 years) with maxillary Little’s Irregularity Index (LII) of 7 mm or more that indicates first maxillary premolars extraction and no medications intake were eligible for this trial. Patients were randomly assigned with 1:1 ratio using simple randomization technique to receive either LLL or placebo treatment. Blinding was applicable for patients only. In the laser group, patients received a single LLL dose (wavelength 830 nm, energy 2 J/point) in four points (2 buccal, 2 palatal) for each maxillary anterior tooth root. Patients in the placebo group had the same laser application procedure without emitting the laser beam. Patients were asked to score spontaneous and chewing pain intensity by filling out a questionnaire with a 100-mm Visual Analogue Scale (VAS) after 1, 6, 24, 48, and 72 h of treatment application. Independent t-test was used to compare the mean pain scores between the laser and placebo groups for both spontaneous and chewing pain at each studied time point. Results No dropout occurred so the results of the 26 patients were statistically analyzed. Despite some clinical differences observed between the two groups, no statistical significance was found for each studied time point ( p  > 0.05) for both spontaneous and chewing pain except after 72 h for chewing pain with a VAS score of (18.84 ± 13.44) mm for the laser group compared to (38.15 ± 27.06) mm for the placebo group. Conclusions LLLT, with the suggested parameters, is not effective in pain reduction following initial orthodontic archwire placement. Trial registration Name of the registry: Clinicaltrials.gov Trial registration number: NCT02568436. Date of registration: 26 September 2015 ‘Retrospectively registered’.

Orthodontic treatment is commonly associated with pain, leading to reduced patient compliance and treatment adherence. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective in reducing this pain by inhibiting prostaglandin synthesis. However, this mechanism may also interfere with orthodontic tooth movement (OTM) by affecting bone remodeling. This narrative review investigates the existing literature published between 2004 and 2024 to assess the impact of various NSAIDs on OTM and identify those that balance pain relief with minimal impact on tooth movement. Evidence shows that NSAIDs such as aspirin, ketorolac, diclofenac, and nimesulide significantly reduce OTM. The results for ibuprofen, meloxicam, and celecoxib were inconsistent with both no influence or a reduction in OTM, depending on dosage, mode, and duration of administration. Conversely, tenoxicam, nabumetone, etoricoxib, and parecoxib appear to have no effect on OTM. Among these, etoricoxib appears particularly promising due to its favorable gastrointestinal profile, high COX-2 selectivity, and negligible influence on OTM in clinical doses. However, the limited number of human trials highlights the need for further research to develop evidence-based guidelines for pain management that preserve treatment efficiency in orthodontics.

Vibration‐assisted orthodontic tooth movement (VA‐OTM) has been promoted as an adjunct with the potential to accelerate treatment, yet its safety profile—together with related tolerability and biological responses—remains uncertain. This harm‐focused systematic review of randomized controlled trials (RCTs) primarily appraised clinical safety end points of VA‐OTM, while explicitly distinguishing these from tolerability/acceptability outcomes and biological response/surrogate markers. The protocol was prospectively registered in PROSPERO (CRD420251166672). Reporting followed the PRISMA‐Harms extension and Cochrane guidance for harms. Major databases and gray literature were searched through August 2025 without restrictions. Eligible RCTs compared intraoral vibration with no adjunct or sham during fixed‐appliance or clear‐aligner therapy. Outcome‐level risk of bias was assessed using RoB 2 and certainty of evidence with Grading of Recommendations Assessment, Development, and Evaluation (GRADE); heterogeneity precluded meta‐analysis, so synthesis was narrative. Twenty‐three RCTs (902 participants) were included. For clinical safety end points, root resorption during canine retraction, including severe resorption (>2 mm), was similar between groups, although one of two premolar tipping studies reported smaller resorption crater volumes with vibration ( p = 0.003). Periodontal indices and tooth mobility generally did not differ between groups ( p > 0.05). For tolerability/acceptability outcomes, vibration did not consistently reduce pain. During fixed‐appliance alignment, one RCT reported lower pain scores with vibration (~1.0–2.3/10 vs. 4.5–6.8/10; p < 0.001), whereas four RCTs showed no significant difference ( p > 0.05). In clear‐aligner therapy, two RCTs showed early reductions in pain ( p < 0.05; p = 0.006) and two did not ( p > 0.05). Oral health–related quality of life and analgesic use showed no clear benefit ( p > 0.05). Biomarker findings were inconsistent: four RCTs reported higher IL‐1β and/or PGE 2 levels with vibration ( p = 0.001, p < 0.05, p ≤ 0.03, and p < 0.001), whereas three found no meaningful change. Most outcome‐level RoB 2 judgments raised some concerns (about 89%), and the certainty of evidence was low to very low for most outcomes. Within these limitations and short follow‐up, adjunctive low‐intensity intraoral vibration appears unlikely to compromise root integrity, periodontal health, or tooth stability, but does not justify routine use primarily for pain control, quality‐of‐life improvement, or root‐resorption prevention; larger, long‐term harm‐focused RCTs with standardized safety outcomes are needed before extrapolating findings to untested devices or dosing regimens.

Background Pain is a common side effect of orthodontic treatment, affecting both patient experience and treatment outcomes. At present, a combination of pharmacological and non-pharmacological therapies is used to alleviate post-orthodontic pain. This study aimed to compare and rank the effectiveness of pharmacological and non-pharmacological interventions for post-orthodontic pain management using a Bayesian network meta-analysis. Methods Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, and the Cochrane Library up to April 2025 for randomized controlled trials evaluating pharmacological or non-pharmacological interventions for orthodontic pain relief. Studies were included if they assessed pain using the Visual Analog Scale (VAS) at 24–48 h. Two reviewers independently screened studies and extracted data, and risk of bias was assessed using the Cochrane RoB 2.0 tool. A Bayesian network meta-analysis was performed to estimate weighted mean differences and rank interventions using SUCRA values. Result A total of 37 RCTs involving 2,430 participants and 16 intervention arms were included. Pharmacological therapies showed greater efficacy than non-pharmacological methods. Etoricoxib and naproxen ranked highest for pain reduction at both 24 h and 48 h, while structured telephone calls, vibration therapy, and low-level laser therapy demonstrated moderate benefits. Discussion Pharmacological interventions—particularly etoricoxib and naproxen—were associated with the greatest pain reduction following orthodontic treatment. Structured behavioral and physical approaches may provide additional benefits. Study limitations included variations in intervention parameters and study quality, which may limit the certainty of evidence.

To assess the effectiveness of diode low-level laser therapy (LLLT) for orthodontic pain control, a systematic and extensive electronic search for randomised controlled trials (RCTs) investigating the effects of diode LLLT on orthodontic pain prior to November 2014 was performed using the Cochrane Library (Issue 9, 2014), PubMed (1997), EMBASE (1947) and Web of Science (1956). The Cochrane tool for risk of bias evaluation was used to assess the bias risk in the chosen data. A meta-analysis was conducted using RevMan 5.3. Of the 186 results, 14 RCTs, with a total of 659 participants from 11 countries, were included. Except for three studies assessed as having a ‘moderate risk of bias’, the RCTs were rated as having a ‘high risk of bias’. The methodological weaknesses were mainly due to ‘blinding’ and ‘allocation concealment’. The meta-analysis showed that diode LLLT significantly reduced orthodontic pain by 39 % in comparison with placebo groups ( P  = 0.02). Diode LLLT was shown to significantly reduce the maximum pain intensity among parallel-design studies ( P  = 0.003 versus placebo groups; P  = 0.000 versus control groups). However, no significant effects were shown for split-mouth-design studies ( P  = 0.38 versus placebo groups). It was concluded that the use of diode LLLT for orthodontic pain appears promising. However, due to methodological weaknesses, there was insufficient evidence to support or refute LLLT’s effectiveness. RCTs with better designs and appropriate sample power are required to provide stronger evidence for diode LLLT’s clinical applications.