Phototherapy versus Occlusal Splint to control painful symptoms in Temporomandibular Disorder : controlled , randomized cost-effectiveness clinical trial

Objective: To compare the efficacy of photobiomodulation and occlusal splint in patients with TMD-associated myofascial pain. Material and methods: 23 patients were randomized into 2 groups: laser group (LG) (n = 12) and occlusal splint group (OSG) (n=11). For the LG, laser was applied to 3 points on each side of the face. Twelve applications were made, 2 sessions per week. In the OSG, patients were instructed to use the device during sleep, 8 hours per night, for a period of 6 weeks, and 12 adjustment and follow-up sessions were performed. Patients in both groups were reevaluated 30 days after the end of the treatments. Results: There was a decrease in pain intensity, according to a visual analogue scale, in both groups before and after 1 month (LG, p = 0.008 and OSG p = 0.002), but with no difference between groups. For the quality of life, both treatments had a positive impact, with this impact being higher in the LG compared to the OSG (p <0.05). Regarding the cost-effectiveness analysis, laser was more cost-effective than the occlusal splint in the clinical trial. The incremental cost of the laser was $3,483.45 compared to the splint, but it had a cost ratio of $4,569.02 for controlled pain intensity while the splint showed $6,691.91 ratio for controlled pain intensity. Conclusion: The photobiomodulation was more cost-effective in controlling painful symptoms in patients with TMD and myofascial pain.


Introduction
According to the American Academy of Orofacial Pain, temporomandibular disorder (TMD) is defined as a set of disorders involving the masticatory muscles, the temporomandibular joint (TMJ) and associated structures. The most common symptoms include facial pain, pain in one or both TMJs and/or pain in the masticatory muscles, headache and earache. As for the signs, they include muscle and TMJ tenderness to palpation, limited and/or impaired mandibular movements and joint noise (Okeson, 2013;Leeuw, 2010).
Orofacial pain is any pain associated with soft and mineralized tissues (skin, blood vessels, bones, teeth, glands or muscles) of the oral cavity and face. This pain can be referred to the head and/or neck region or even be associated with cervical pain, primary headache and rheumatic diseases such as fibromyalgia and rheumatoid arthritis (Leeuw, 2010). TMDs are the most common non-dental cause of orofacial pain (Pozzebon, 2015), and muscle pain is the main complaint reported by patients with TMD, being associated with the feeling of fatigue and muscle tension, ranging from mild to extreme discomfort (Okeson, 2013). Having to live with pain is a very uncomfortable condition for any individual. Pain impairs physical and mental function and results in costly treatments and reductions of productivity and quality of life (Basto et al, 2017). treatment of TMD-related pain due to its analgesic and anti-inflammatory effects (Morais Maia et al., 2012;Dostalová et al., 2012;Cavalcanti et al., 2016;Melchior et al., 2016;Panhoca et al, 2013). A major advantage of LLLT for TMD is that it is a non-invasive, lowcost therapy that is currently being widely used in dental practice, reducing the need for surgery or the use of drugs for pain relief and tissue regeneration (Kato et al, 2006;Fikackova et al., 2006).

Materials and Methods
The purpose of this study was to carry out a comparative analysis of the effectiveness and costs of phototherapy and occlusal splint therapy in patients with TMD through a controlled and randomized clinical trial. This is a prospective trial with a clinical and economic approach. Study activities were carried out on the premises of Nove de Julho University Clinical School of Dentistry. The study followed regulatory and ethical standards for human research and was submitted to the Research Ethics Committee of Nove de Julho University, having been given a favorable opinion (Opinion Number: 2.014.339). For being a clinical trial, the study was also registered in the ClinicalTrials.gov Identifier: NCT03096301 (March 9, 2017). Patients were instructed on study procedures and data collection was started after subjects had signed the informed consent form.
Patients aged 15 to 25, screened at UNINOVE Clinical School of Dentistry entered the study. Thirty patients were screened following the sample calculation based on studies with LLLT and occlusal splint, using DINAM 1.0 software (Godoy et al., 2013). For the diagnosis of TMD, the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) (Pereira-Júnior et al., 2004) questionnaire was applied before any intervention.
The inclusion criteria included young people aged 15 to 25 years, with a diagnosis of TMD in group I (myofascial pain according to RDC-TMD) and also with a diagnosis of TMD in group I associated with group IIa (disc displacement with reduction). Individuals with dentofacial anomalies, who were undergoing maxillary orthodontic or orthopedic treatment, or under psychological and/or physical therapy were excluded. Subjects using myorelaxant or anti-inflammatory medications were also excluded. Subjects screened were assigned to 2 groups: Laser Group (LG) (n = 15) and Occlusal splint Group (OSG) (n=15). For the random distribution of subjects with TMD, randomization was carried out by draw, using research randomizer software. Research, Society and Development, v. 9, n. 11, e66991110251, 2020 (CC BY 4.

Clinical Procedures
For low-power laser therapy, indium-gallium-aluminum phosphate (In-Ga-Al-P) device, by THERAPY EC, (DMC®, São Carlos, SP, Brazil) was used, with infrared wavelength of 808 nm ± 10 nm and 100 mW power, properly calibrated. Twelve laser applications were performed, two sessions per week. The 808nm wavelength with 100mW power was used for 60 seconds per point, resulting in a total energy of 6J per point (Table 1).
Application was specific, in contact with the skin and with a conventional tip, according to the protocol suggested by Shobha et. al (2017) and Ahrari et al. (2013). Laser was applied to 3 points of the masseter muscle (upper, middle and lower bundles) and 1 point in the anterior temporal muscle on each side of the face (Venezian et al., 2010;Carvalho et al. 2009 The group receiving occlusal splint therapy was instructed to use the device during sleep, 8 hours a night, for a period of 6 weeks, plus 1 month after treatment. The splints were made following the principles established by Okenson (2013). In the upper model, a 2 mm Research, Society and Development, v. 9, n. 11, e66991110251, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i11.10251 7 acetate splint was made to be subsequently produced with acrylic resin (Botelho, 2012). and was centrically adjusted to promote occlusal stability and disocclusion guidance. Monitoring and adjustments were performed whenever necessary, during the evaluation period until the end of treatment (Botelho, 2012;Pomponio, 2010). Muscle pain was assessed using the clinical criteria of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Clinical examination was performed at baseline and 1 month after treatment. To assess the impact of treatment on the subjects' quality of life, an EQ-5D-3L instrument was used, which consists of two stages, a questionnaire and a visual analogue scale (VAS). The instrument was applied at baseline and 1 month after treatment. Responses were compared between groups.

Economic Procedures
In this study, a cost-effectiveness analysis of both groups studied was carried out and for that, it was necessary to obtain the cost-effectiveness data of each therapy. The study followed the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), which are specific for reporting economic evaluation studies. Direct costs in both groups were calculated by adding the amount of each material used in each group (Silva et al., 2017) Sobral et al. (2017).
In order to make it possible to compare TMD treatment costs and generalize the results of this economic study to other countries, US dollar was used as common reference (calculated based on the Central Bank website on November 1, 2019, of US$ 39,786). The effectiveness of both treatments will be measured by assessing pain and quality of life.

Data Analysis
To analyze clinical trial data, data distribution was assessed using the Kolmogorov-Smirnov test and it was found that the variables had a normal distribution. To compare both groups studied before and after treatment, t-paired and two-way ANOVA tests were used, complemented by Bonferroni. For all analyses, a statistically significant difference of α= 0.05 was considered. Data were analyzed using the SPSS 23.0 statistical package (IBM Corporation).

Pain Outcome Analysis
Pain was assessed using RDC/TMD at the baseline (before treatment) and 1 month after the end of treatment. Pain data of patients with TMD included in the study had a normal distribution. Table 2 shows comparison data for both treatments, where we observed a statistically significant difference in terms of pain reduction between the laser and the splint groups before and 1 month after treatment for the following parameters: overall facial pain (1.455* / p<0.0001), right side pain (1.455* / p<0.0001) and left side pain (1.000 / p=0.009), with laser therapy showing superior results compared to the occlusal splint. Laser therapy also showed superior and statistically significant results compared to occlusal splint therapy for the following parameters: maximum mouth opening without (4.727* / p<0.0001) and with assistance (4.000* / p<0.0001), and joint pain (1.091 * / p=0.010). The occlusal splint group showed superior results compared to the laser group for the following parameters: muscle pain (0.909* / p=0.047) and VAS right temporal muscle (0.364 * / p=0.048).

Outcome of Quality of Life Analysis
The impact of treatment on the quality of life of patients with TMD was measured using the EQ-5D-3L instrument, where 0 represents the worst health status and 100 the best one. Table 3 shows data regarding comparison between groups before and 1 month after treatments.
When treatments were compared, an improvement in patients' health status was observed in both treatment groups, the laser group (17,500*) and the occlusal splint group (11,818*), before and 1 month after treatment. Laser therapy (p=0.011) showed a superior and statistically significant improvement when compared to the occlusal splint group (p=0.084).
Therefore, both treatments were effective in improving patients' quality of life. However, laser therapy provided a more significant improvement.

Sample Effect Size
The size of the sample effect reflects the magnitude of the difference between the experimental and control groups. Effect measurements were defined by Cohen at three levels:

Cost-Effectiveness Analysis: Pain and Quality of Life
For the cost-effectiveness calculations, US dollar ($) was used and for the effectiveness calculations, pain and quality of life outcomes were used.
In this paper, the measurement unit of effectiveness was characterized by the clinical performance of treatments; for the Pain and Quality of Life Outcomes, the difference in the mean scores before and 1 month after treatments was considered "Clinical Success": Laser Group -Pain = 1.33 / Quality of life = 17.50 and Occlusal splint Group -Pain = 0.45 / Quality of Life = 11.81 The randomized clinical trial provides accurate information for calculating the costeffectiveness ratio. Table 4 shows treatment costs in the laser and occlusal splint groups for the Pain outcome. ICER (incremental cost-effectiveness ratio), that is, the incremental cost per unit of benefit obtained, was calculated for both groups studied with the Pain and Quality of Life Outcomes. ICER was calculated considering the cost of treatment in 12 sessions and considering the difference in the mean scores before and 1 month after treatment in the Laser Group and Occlusal splint Group.
The incremental cost for the Pain outcome in this study is $3,483.45; whereas for the Quality of Life outcome, it is $538.74. The cost-effectiveness ratio in the laser and splint groups was $4,569.02 and $6,691.91 / per controlled pain intensity, respectively. This shows that laser therapy was more cost-effective than splint treatment in controlling pain in patients Research, Society and Development, v. 9, n. 11, e66991110251, 2020 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v9i11.10251 13 with TMD. As for Quality of Life, cost-effectiveness in the laser group was $347.24 and in the splint group it was $254.98 / per impact on quality of life. Although the splint group is more cost-effective regarding the positive impact on patients' quality of life, we can see that for the same time interval, the laser group had a greater number of patients with clinical success when compared to the splint group.

Discussion
The American Academy of Orofacial Pain defines TMD as a set of disorders involving the masticatory muscles, the TMJ and associated structures. TMD is the second most common type of orofacial pain, with an estimated prevalence of 3 to 15% of the population (Bender, 2014).
The studies by Dantas et al. (2015) and Cordeiro et al. (2012) showed that more women than men look for a specialized service in orofacial pain and that the patients evaluated showed TMD and high emotional tension. These findings support the data found in this study, where 91.3% of the patients included in the research study are female.
The studies by Maia et al. (2012);Fikáckova et al. (2007); Shirani et al. (2009);and Ahrari et al. (2013) confirm the results of this study regarding significant improvement in muscle pain in patients of the laser group (12 treatment sessions) when the periods before and after treatment are compared. Reduced pain sensitivity can be justified due to the cumulative effect of low-power laser and modulation of the inflammatory process (Carrasco et al. 2008).
In this clinical study, both laser and occlusal splint treatments improve patient's pain and mouth opening when comparing the periods before and 1 month after treatment, but there was no statistical difference between the groups. Demirkol et al. (2015) evaluated the effects of LLLT and the use of occlusal splints in patients showing signs and symptoms of TMD with myofascial pain according to RDC/TMD. Thirty subjects were screened and assigned to 3 groups: occlusal splint, LLLT, and placebo.
Pain intensity values were observed to have been reduced after treatment in both groups (LLLT and occlusal therapy) compared to the placebo group that did not show statistical differences. The authors concluded that the specific dosage in LLLT was as effective as the occlusal splint therapy in reducing pain in individuals with TMD who had myofascial pain.
The study by Oz et al. (2010) evaluated the effects of low-level laser and occlusal splint to treat patients with signs and symptoms of myofascial TMD. A total of 40 patients were randomly assigned to 2 groups: laser and control (occlusal splint). Comparisons were made within and between groups before and after treatment. Vertical movements showed statistically significant improvements after treatments in both groups, but when the groups were compared, there was no significant difference between them. In both groups, tenderness to muscle palpation decreased significantly. Assessments of pressure pain thresholds and VAS scores also revealed similar results. It was possible to conclude that laser therapy is as effective as the occlusal splint therapy in improving pain and jaw movements in patients with myofascial TMD. This clinical trial showed that laser therapy improved patients' quality of life, and proved to be superior and statistically significant when compared to the improvement offered by the occlusal splint treatment.
Cost-effectiveness calculation showed that laser therapy was more cost-effective than the splint treatment in controlling pain in TMD patients. Regarding Quality of Life, costeffectiveness of the laser group showed a higher value for impact on quality of life than the occlusal splint group. Although the splint group is more cost-effective in relation to positive impacts on patients' quality of life during the same time interval, laser therapy showed a greater number of patients with clinical success when compared to the occlusal splint group.

Conclusions
The controlled and randomized clinical trial conducted found that laser and occlusal splint treatments were effective in reducing pain in patients with myofascial TMD. It also found that there was no statistically significant difference in some of the variables related to pain reduction in patients with TMD when comparing laser and occlusal splint therapies. In the Quality of Life outcome, both treatments (laser and occlusal splint) were effective in improving patients' quality of life. However, when treatments were compared, laser therapy was more effective than the occlusal splint. Regarding the cost-effectiveness analysis, laser therapy was more cost-effective than the occlusal splint in this clinical trial.
A limitation of the present research was to evaluate the patients only 01 month after the end of the treatments, as TMD is complex, we could have followed the patients for a longer period of time, which could better reflect some difference between the groups.
As a suggestion for future research, we have the measurement of pain with VAS, immediately after each laser application.