Summary Background No randomized controlled trial before has evaluated the role of low-level laser energy in its analgesic effects in orthodontics. Objective To evaluate the effect of single application of low-level laser with 4-Joule or 16-Joule energy on pain reduction following elastomeric separators placement. Trial design A two-arm parallel-group single-blind placebo-controlled randomized controlled trial, with implementation of split-mouth technique in each group. Materials and methods Twenty-six patients in need of orthodontic treatment with a fixed orthodontic appliance were enrolled and randomly allocated to either the 4-Joule or the 16-Joule laser energy group. Elastomeric separators were applied for the mandibular first molars. For each patient one molar received a single low-level laser dose using an 830-nm Ga-Al-As laser device with either 4-Joule or 16-Joule laser beam energy, while the other molar received a placebo treatment by applying the laser device in the same method and parameters as the counterpart molar without emitting the laser beam. The molar to be irradiated was also randomly chosen using simple randomization technique. Allocation was concealed and patients were blinded to which side would receive the laser irradiation. Main outcome measure was the degree of pain scored during mastication for each mandibular first molar after 1, 6, 12, 24, 48, and 72 hours of both laser and placebo treatments application. A questionnaire with an 100-mm Visual Analogue Scale (VAS) was used for pain assessment. Results Thirty-six patients were evaluated for eligibility, 10 of them were excluded making the final randomized number 26 patients. One patient dropped out later for not completing the questionnaire. Accordingly, the results of 25 patients were statistically analysed. No statistical significance was found for both low-level laser energy values in comparison to the corresponding placebo treatments. No harms were encountered. Limitations Intervention provider was not blinded to the intervention. Conclusion Low-level laser therapy, applied at two different laser energy values, is ineffective in relieving elastomeric separators induced orthodontic pain. Trial registration This trial was not registered. Funding No funding to be declared. Introduction Orthodontic treatment involves the application of various forces to the periodontal ligament throughout its several phases, consequently making the orthodontic treatment a painful procedure (1). Pain associated with the different phases of orthodontic treatment is one of the main setbacks discouraging patients from undergoing orthodontic treatment (2–4). An estimated 8 to 30 per cent of orthodontic patients refuse to continue their orthodontic treatment because of pain associated problems (5). Furthermore, 50 per cent of orthodontic patients have difficulties in mastication function because of their orthodontic treatment (6). In order to provide proper space for the insertion of orthodontic bands, orthodontists usually insert elastomeric separators to the mesial and distal of the tooth to be banded. Elastomeric separators placement is considered a painful procedure for approximately all patients (7). Applying elastomeric separators generates pressure in the periodontal ligament which leads to the secretion of inflammatory mediators, like prostaglandins and histamine, that stimulate free nerve endings resulting in the perception of pain (5, 8, 9). Different methods have been studied in order to reduce orthodontic pain. The principal method relied mainly on medications especially Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as Ibuprofen (10). Despite their effectiveness, these medications have some systemic side effects including gastric and duodenal ulceration, coagulation disorders, congestive heart problems and allergic effects that limit their use in many cases (8), in addition to their important side effect on orthodontic treatment which is reducing the orthodontic movement rate (11). A non-pharmacological method called Low-Level Laser Therapy (LLLT) has been recently studied and showed to be effective without any obvious side effects (12). LLLT is a physical method that utilizes a special device to generate a coherent light beam within a specific wavelength range (13). This method proved to be efficient in orthodontics either through its photobiomodulation effect, which has been shown to accelerate orthodontic tooth movement (14) or its analgesic and anti-inflammatory effects (7). The analgesic effect of LLL is assumed to be the result of several mechanisms, which involve raising the body’s surface temperature, increasing the local blood flow which leads to the removal of pain-inducing substances (15), stimulating the production of Adenosine Triphosphate (ATP) molecules (16), inhibiting the secretion of inflammatory substances and inducing the release of neurotransmitters in targeted tissues (17–20). Many investigators studied the efficiency of LLLT in reducing orthodontic pain after elastomeric separators placement (3, 7, 12, 13, 21–24), after first orthodontic archwire engagement (4, 25) or during canine retraction (2). Results of those studies varied between some supporting LLL effectiveness (2–4, 7, 12, 22, 25) or others rejecting it (13, 21, 23, 24). These different outcomes may have been resulted given that each study used a specific LLL protocol that varied in the wavelength, energy, irradiation dose and application time (12), which led to different results. From the previous parameters, LLL energy is considered a decisive factor in its effect on pain reduction (26). New systematic reviews concluded that LLL is considered a promising technique for orthodontic pain reduction, yet the evidence is still minimal with the need for more well-designed studies to prove its efficiency (17, 27, 28). Therefore, the objective of this study was to investigate the effect of single application of LLL on orthodontic pain caused by elastomeric separators placement using two different energy values (with all other parameters unified) in order to determine the role of LLL energy in its effectiveness given that no previous study has investigated this aspect. The null hypothesis is that LLL is ineffective in orthodontic pain reduction with both studied energy values and that the laser energy does not affect its efficiency in pain reduction. Materials and methods Trial design This study was a two-arm parallel-group single-blind placebo-controlled randomized controlled trial. The split-mouth technique was implemented for each group in order to apply laser and placebo treatments for each patient. The study was conducted at the Department of Orthodontics and Dentofacial Orthopaedics and the Laser Research Unit at the Faculty of Dental Medicine, Damascus University, Syria, between April 2016 and August 2016. The CONSORT statement was used as a guide for this study (29). Ethical approval was obtained from the ethics committee at the Ministry of Higher Education in Syria. Sample size calculation Sample size calculation was done using G*power 3.1.3 program. Depending on data from Nobrega et al. study (3), and assuming a study power of 95 per cent and a significance level of 0.05, the sample size for each group according to the program was 12 patients. Taking into consideration sample attrition, an additional patient was added to each group which made the total sample size 26 patients. Participants and eligibility criteria Twenty-six patients (7 males, 19 females) participated in the study. Patients were scheduled to have orthodontic treatment with a fixed orthodontic appliance. Informed consent was taken from each participant after a thorough explanation of the study aims and methods. The inclusion criteria were as follows: patient age is between 16 and 22 years, good oral hygiene, no systemic or periodontal diseases, no intake of medications that interfere with pain perception for at least one week before the beginning of the treatment, intact mandibular first molars and the presence of healthy contact points of the mandibular first molars with adjacent teeth. The exclusion criteria were the intake of NSAIDs or analgesics during the study, failing to complete the questionnaire and patient who received previous orthodontic treatment. Participants were enrolled by the corresponding author. Randomization Patients were randomly assigned to either the 4-Joule laser energy group or the 16-Joule laser energy group with allocation ratio of 1:1 using a simple randomization technique. Each patient was asked to choose one white closed paper from a black opaque box containing 26 white closed papers, half of which had the number 4 written while the other half had the number 16 written. According to the chosen paper, the laser beam energy to be applied was determined. The molar to be irradiated was also chosen randomly by asking each patient to choose a number representing the molar to be irradiated: 1. which indicates the right molar or 2. which indicates the left molar. The other molar received the corresponding placebo treatment. Allocation was concealed from both the intervention provider and patients. Random allocation sequence generation, patient assignment to interventions and the allocation concealment were implemented by the co-authors. Clinical interventions A 0.5-mm elastomeric separators (Ortho Classic, 1300 NE Alpha Drive, McMinnville, Or, USA) were inserted at the mesial and distal of each mandibular first molar. For the molar to be irradiated, a single LLL dose was applied using a Ga–Al–As semi-conductor laser device of the continuous emission mode (CMS Dental ApS, 55 Wildersgade, 1408 Copenhagen K, Denmark) with a wavelength of 830 nm and a power of 150 mW. One of two laser energy values was applied for each patient: 13 patients received 2 J/point laser energy with an irradiation dose of 2.25 J/cm2 and an exposure time of 15 seconds/point, and the other 13 patients received 8 J/point laser energy with an irradiation dose of 9 J/cm2 and an exposure time of 60 seconds/point. Laser beam was applied to one point on both the mesial and distal sides of the molar at the level of the cervical third of the root, perpendicular to the mucosa and in direct contact with it (Figure 1). Application was done on the buccal side only resulting in two application points for each molar with total laser energy of 4 J/molar for the first group (the 4-Joule laser energy group) and 16 J/molar for the second group (the 16-Joule laser energy group). Figure 1. View largeDownload slide Low-level laser application. Figure 1. View largeDownload slide Low-level laser application. Placebo treatment was implemented by applying the laser device to the other mandibular first molar with the same manner and exposure time as for the irradiated molar by turning on the device without emitting the laser beam to obtain the placebo effect. Allocation was concealed from patients so that they did not know which molar would be irradiated and which one would receive the placebo treatment in order to keep them blinded to the intervention. Outcome measure The main outcome measure was the degree of pain scored during mastication for each mandibular first molar at specific time points following the application of the laser and placebo treatments. Evaluation was done using a questionnaire containing an 100-mm Visual Analogue Scale (VAS) for each time point, with the number 0 indicating no pain and the number 100 indicating the worst possible pain. Laser and placebo treatments were applied at approximately the same time of the day (12 P.M. ± 1/2 hour) for all patients, so that the later evaluation time points were also unified among them. Each patient was given a questionnaire containing the evaluation time points (after 1, 6, 12, 24, 48, and 72 hours of treatments application). At each defined evaluation time point, the degree of pain was scored twice, one for each mandibular first molar to assess the effect of laser and placebo treatments on the degree of pain perception. Patients were instructed on how to record their pain degree and were recommended to score the pain degree exactly at the defined time in order to get the precise score. At each evaluation time point patients were instructed to bite on a piece of bread on both sides—which requires a degree of pressure to be chewed—in order to stimulate the mastication procedure and provoke the pain and then to score the degree of pain for each molar separately. Harms No harms were encountered. Statistical analysis Data were statistically analysed using SPSS program version 20 (SPSS Inc, Chicago, USA). According to Kolmogorov–Smirnov test, the data were normally distributed. The paired t-test was used to compare the mean pain scores between laser and placebo treatments in each of the two studied laser energy groups. Results Participants flow The CONSORT flow diagram is shown in Figure 2. 36 patients were initially examined for eligibility, 10 of them were excluded resulting in 26 patients that were randomly allocated to either the 4-Joule or the 16-Joule laser energy group. One patient from the 4-Joule laser energy group dropped out for not completing the questionnaire. Eventually, data from 25 patients were used for the statistical analysis. Figure 2. View largeDownload slide CONSORT flow diagram. Figure 2. View largeDownload slide CONSORT flow diagram. Sample characteristics are shown in Table 1. Table 1. Sample characteristics. N Gender Age (years) Male Female Mean SD 4-Joule laser energy group 12 3 9 18.16 1.69 16-Joule laser energy group 13 4 9 18.38 1.75 Total sample 25 7 18 18.28 1.69 N Gender Age (years) Male Female Mean SD 4-Joule laser energy group 12 3 9 18.16 1.69 16-Joule laser energy group 13 4 9 18.38 1.75 Total sample 25 7 18 18.28 1.69 View Large Main findings Figure 3 shows the mean pain scores of the 4-Joule laser energy group. No statistical significance was found between the laser and the placebo treatments for each evaluation time point, indicating that LLL at this energy value has no effect in pain reduction. Figure 3. View largeDownload slide Mean pain scores of 4-Joule laser energy group (mm). Figure 3. View largeDownload slide Mean pain scores of 4-Joule laser energy group (mm). Furthermore, the difference in mean pain scores between the laser and placebo treatments was not statistically significant in the 16-Joule laser energy group also, indicating that LLL is ineffective in reducing pain with the 16-Joule laser energy. Results are illustrated in Figure 4. Figure 4. View largeDownload slide Mean pain scores of 16-Joule laser energy group (mm). Figure 4. View largeDownload slide Mean pain scores of 16-Joule laser energy group (mm). In both groups, the peak of pain was observed after 24 hours with mean pain scores of (28.33 ± 22.49) mm and (37.5 ± 22.1) mm for laser and placebo treatments respectively in the 4-Joule laser energy group and (41.92 ± 28.25) mm and (43.46 ± 23.75) mm for laser and placebo treatments respectively in the 16-Joule laser energy group. Discussion This study aimed to evaluate the effect of applying LLL with two different energy values on reducing orthodontic pain caused by elastomeric separators placement. It was found that LLL with both energies used was not effective in reducing orthodontic pain. The importance of the study Many previous studies evaluated the effect of LLL on reducing pain caused by elastomeric separators placement (3, 7, 12, 13, 21–24). However, since different protocols and parameters were used, the results varied between supporting (3, 7, 12, 22) or rejecting (13, 21, 23, 24) LLL effectiveness. Hence, it was not possible to exactly determine each parameter role in LLL effectiveness, so this point—which has not been studied by any previous study before—requires further investigation. Furthermore, according to systematic reviews there is still a need for well-designed randomized controlled trials to define the exact role of each LLL parameter in its effect on orthodontic pain reduction (9, 26). Therefore, this is the first study that evaluates the role of LLL energy by studying the use of two LLL energy values (with all other parameters unified) to determine the effect of this important LLL parameter on the efficiency of this approach. Factors affecting LLLT results Ren et al. stated that the results of studies investigating orthodontic pain reduction using LLL depend on three principle factors: individual variations, study methodology and laser beam parameters (17). Some investigators postulated that pain assessment is affected by many individual factors including age, gender, psychological state, pain threshold, previous pain experience, the emotional state and the importance of placebo effect (30). The results of previous studies showed no effect of age (6, 21) and gender (7, 21) on pain scores. One of the important individual factors is the pain perception threshold which may highly differ among patients. The VAS used for pain assessment in this study is considered an important method for reducing the effect of this factor especially when a large variability is expected (31). Individual factors may also include different tissue responses toward the laser beam effect which may have its impact on the results and could explain the differences in the results among various studies even when similar protocols and parameters are used. Another method to avoid the effect of individual variations especially the difference in pain perception threshold among patients is applying the split-mouth technique. In this study this technique was applied in each laser energy group in order to deliver both the laser and the corresponding placebo treatments for each patient which helped in eliminating any negative effects of the individual factors on pain assessment accuracy. However, applying this technique prevented the comparison of two laser beam energies in the same patient given the differences in treatment exposure time that result from the settings of the laser device, in which the exposure time increases with the increase of laser energy, thus leading to the use of the other mandibular first molar for the placebo treatment. The difference in exposure time also eliminates the merge of the results of placebo treatments from both laser energy groups into one group, as this might affect the patient’s decision regarding the pain score. For that reason, each laser energy group had its own placebo treatment to be compared with. Patients were blinded toward which side would receive the laser treatment. Blinding of individuals is also considered a very important method for eliminating the effect of individual factors on the accuracy of pain assessment (32). In this study, pain was evaluated during the mastication procedure. Many studies proved that pain problems with orthodontic treatment emerges during function - especially during the chewing of foods - rather than it being spontaneous, forming the most difficult deterrents for patient’s activities (33). Besides, most studies evaluated spontaneous pain perception and only few evaluated pain perception during function (3, 22). The method used to provoke pain during mastication and the treatments’ application time were unified among all patients to ensure they followed the same criteria for a precise reporting of their degree of pain, given that the perception of pain is influenced by diurnal fluctuation associated with daytime (34). The results of this study should be discussed only with the results of studies that evaluated pain after elastomeric separators placement because it involves evaluating the pain score for one tooth only compared to evaluating pain for many teeth like in leveling and alignment stage which might exaggerate the degree of pain (25). For a precise evaluation of the effect of LLL energy, the laser beam was concentrated in one point for both the mesial and distal sides of the mandibular first molars on the buccal side only, taking into consideration the positive results of some studies with buccal application only (3, 12). However, other studies with one-sided application did not detect positive effects of LLL (23, 35). A possible explanation could be that a one-sided application may leave areas of the periodontal ligament with no stimulation of biological procedures that eventually leads to the occurrence of pain, compared to positive results found with both buccal and palatal/lingual sides laser application which cover the periodontal ligament completely (7, 36). Despite that, some studies found no effect even with a two-sided application (24). A single application was used to make the application protocol practical since it does not need many appointments to achieve and does not depend on the patient’s cooperation. This application method was shown to have positive results in some studies (3, 36) while it was not effective in others (13, 23) which is in line with the results of this study. Some investigators used multiple applications protocol and also found different results that support (7) or deny (21, 35) the laser effect in pain reduction. However, the accumulative effect resulting from multiple applications may give this method superiority over single application since it leads to inhibiting the nerve endings after a definite threshold according to Arndt-Schulz law (37). Laser parameters in this study were unified between the two groups except for the laser energy to precisely evaluate the role of this parameter in laser effect on pain reduction. A 2-J/point energy was chosen for the first group. Sousa et al. stated that the probable recommended energy value for LLL to be effective in orthodontic pain reduction is 1–2 Joules when one tooth is irradiated (26). This low energy is supposed to have positive effects on pain reduction according to some previous studies’ results (3, 7, 36) because it falls in the recommended energy range which affects the tissues and could result in the desired biological effects which may then lead to pain reduction. However, this study found no analgesic effects of the 2 J/point energy which may resulted from the single application of the laser beam or its application from one side that consequently hide the possible positive effect of LLL with this energy value. This result agrees with some studies’ results (23, 24, 35) and disagrees with others (3, 36). The other energy value used for the second group was 8 J/point, which is relatively much more higher in order to examine the efficiency of high energy values in pain reduction since no previous study has evaluated that before. Similar to the 4-Joule laser energy, no effect was observed when the 16-Joule laser energy was used. Furthermore, the results showed close degrees of pain scores between the laser and the placebo treatments in the 16-Joule laser energy group, especially after 6 hours of treatments application when the recorded pain scores were significantly lower in the placebo group compared to the laser group. A possible explanation for this effect could be that this relatively higher energy of the laser beam concentrated in two points exceeded the therapeutic window which may lead to local destruction and photoinhibitory effect in the targeted tissues leading to negative reactions in them (17), which may indicate that the 16-Joule laser energy value is too high and may provoke additional pain instead of reliving it. The wavelength used was 830 nm which falls within the recommended LLL wavelength range of 500–1200 nm (25) and guarantees the penetration of the laser beam deep into tissues, which is considered important to get the positive effects of LLL (38). This wavelength also showed positive results when applied in previous studies (3, 36), compared to other studies’ results that used lower wavelength values like 635 nm (21) and 660 nm (13) and found no effects. The type of laser used was Ga–Al–As semi-conductor diode laser. Most studies use this type because these lasers showed to have positive biological effects on targeted tissues. Only one study evaluated the use of surgical lasers, applying CO2 laser which has a very high wavelength (between 9300 and 10600 nm) (39). Although positive results were found, the use of these lasers may not be practical for routine use. A continuous emission mode was utilized in this study as all previous studies use this emission mode, except for Marini et al. study in which a superpulsed emission mode was used and showed positive results (40). Comparisons with previous studies The peak of pain was observed after 24 hours in both the 4-Joule and the 16-Joule laser energy groups. These results coincide with the results of other studies which also found that the pain peaked after 24 hours of elastomeric separators application (21, 36). In general, comparing the results of this study to the results of studies that have used similar LLL protocols, it seems that the results are widely conflicted among studies. Nobrega et al. evaluated the single application of an 830-nm wavelength laser beam to four points on the buccal side only with 5 J/tooth energy and found positive effects in pain reduction (3). Artes-Ribas et al. used the same wavelength with single application on both sides and 2 J/point energy and found similar results (36). This contradiction with the results of this study may be due to the application of laser beam on both sides or using application points that cover the whole periodontal ligament which both enable the laser beam to reach all nerve endings and cause the desired effect. On the contrary, Furquim et al. evaluated the single application of an 808-nm wavelength laser beam to 3 points on the buccal side only with 6 J/tooth energy (23) and Lim et al. applied an 830-nm wavelength laser beam with three different low laser energy values on a daily basis for 5 days (35) and the results from both studies found no effects of LLL in pain reduction, in agreement with this study’s findings. Limitations No blinding was applied for intervention provider. This is due to the roles of our institution that forces the corresponding author to deliver the intervention himself/herself. However, in almost all previous studies intervention provider was not blinded, and concealing the allocation from the intervention provider helped in eliminating any possible bias risk. Generalization According to the results of this study we can conclude that LLL energy (especially high doses) does not have effect—as previously postulated—on LLL effectiveness in reducing orthodontic pain after elastomeric separators placement. However, we cannot generalize that LLL is not effective at all in reducing orthodontic pain because changing other parameters like the wavelength or even changing the application protocol like the exposure time per point or the frequency of laser application might lead to effective results. Conclusions Single application of 4-Joule or 16-Joule Ga–Al–As low-level laser therapy was ineffective in reducing orthodontic pain caused by elastomeric separators at the mandibular first molars. Funding None. Authors' Contributions The correspondent author contributed to study design, implementation of interventions, data collecting, analysis and interpretation, and drafted the manuscript. 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The European Journal of Orthodontics – Oxford University Press
Published: Feb 1, 2018
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