Temporomandibular disorder, body pain and systemic diseases: assessing their associations in adolescents

Abstract Painful temporomandibular disorders (TMD) in children and adolescents may impact negatively the individual´s life. The presence of comorbidities associated with TMD tends to increase the persistence of pain and to facilitate its chronification. Objective To investigate the presence of other painful conditions and systemic diseases and their association with painful TMD. Methodology In this cross-sectional study, 690 adolescents aged between 12-14 years old were evaluated through questionnaires and clinical examinations. Results Painful TMD was found in 16.2% of the sample, with a significant association with bronchitis (OR= 2.5; p=0.003) and asthma (OR=3.1; p=0.013), reported by the parents/legal guardians of the participants. Adolescents with regional and widespread pain were 2.7 (95% CI: 1.65-4.55) and 3.6 (95% CI: 1.29-10.14) more likely to also present painful TMD. Painful TMD was associated with a higher number of body pain sites in the last 12 months (4.26 vs. 2.90; p<0.001), as well as a higher number of systemic diseases (1.48 vs. 1.18; p=0.048), when compared to adolescents without painful TMD. Conclusion The findings of this study point out the importance of considering the presence of comorbid conditions in the diagnosis and management of painful TMD in adolescents. A multidisciplinary approach would contribute to better control of painful TMD and decrease its chronification risk.


Introduction
Adolescence is a complex phase of life when individuals experience intense emotional, cognitive, social, physical, and hormonal transformations. It is also the period in which the behavioral traits are defined. 1 Occurrence of pain at this stage can be associated with disability and a predictive factor for pain in adulthood. 2 Anxiety, depression, reduced quality of life, and school absenteeism are conditions frequently present in adolescents with somatic pain. 3 These experiences represent significant risk factors for the development of chronic pain in the later stages of life. Therefore, a better understanding of pain features in this age group is fundamental to define more efficient treatment protocols as well as to prevent future health problems. 2,4 Temporomandibular disorders (TMD) are defined as a group of musculoskeletal and neuromuscular conditions involving temporomandibular joints (TMJs), masticatory muscles, and associated structures. Pain is the most frequent symptom and can affect both muscles or joints. 5 Although TMD has been more investigated in adults than in adolescents, recent studies have pointed to an increase in its prevalence among the latter, with rates ranging from 7.3% and 30.4%. 6 The complexity of TMD is enhanced by its association with other painful conditions as headaches, neck pain, and back pain. 7 Moreover, the emotional and psychosocial aspects can influence the painful experience related to TMD. 8,9 Previous studies investigated the prevalence of headache, abdominal pain, low back pain and TMD in children and adolescents, [10][11][12]   in adolescents". So far, two previous papers were published, presenting part of the collected data. 16,17 Each of them, although based on the same sample, had specific aims, and consequently, different instruments and evaluations were applied. For this reason, it is recommended to calculate the sample size separately for each of the primary outcomes by applying a Bonferroni correction to adjust the significance level.
Thus, for the sample size calculation, we considered the prevalence obtained in the pilot study, a statistical power to refute H0 of 80%, and alpha of 0.007, adopted after Bonferroni correction, according to our goals. 18 Accordingly, the sample should consist of approximately 120 individuals with painful TMD and 120 individuals free of painful TMD. Also, we added 25% due to possible losses during the data collection, thus totaling a minimum of 300 participants in the study. The investigation of the association between systemic diseases and painful TMD was an exploratory analysis.

Assessment instruments
The family economic classification was determined according to the updated Brazilian Classification  days. The body areas were grouped in regional pain (neck/shoulder) and widespread pain (upper back, elbows, wrists/hands, lower back, hips/thighs, knees and ankles/feet). 23 Parents or legal guardians of adolescents responded a questionnaire about the current medical condition, considering a previous medical diagnosis. This information was collected and evaluated in a list, which was presented to legal guardians, containing the most frequent diseases reported among Brazilian youth. 24 These diseases were grouped as follows : 1) Respiratory diseases (bronchitis, rhinitis, asthma, sinusitis, pulmonary emphysema, and pneumonia); 2) Gastrointestinal diseases (gastro-esophageal reflux; irritable bowel syndrome, constipation, gastritis/ ulcer, and colitis); 3) Endocrine diseases (diabetes, hypothyroidism, hyperthyroidism, and hypoglycemia);  of having painful TMD compared with individuals free of these respiratory conditions ( Table 2). Adolescents reporting regional pain were 2.7 (95% CI: 1.65-4.55) more likely to present painful TMD when compared to those who did not report regional pain. When the areas of regional pain were      (Table 3). Moreover, adolescents presenting painful TMD reported a significantly higher number of body pain areas in the last 12 months compared with adolescents with no painful TMD (p<0.001). They also reported a significantly higher number of systemic diseases (p=0.048) ( Table 4).

Discussion
TMD has been associated with several painful and non-painful conditions in adults. 14,15,23 Additionally, it has been demonstrated that the presence of comorbidity tends to increase the severity and the disability related to the involved conditions, as well as make worse their prognostic. 7 Because there is a lack of information regarding the associations between TMD and other conditions among adolescents, our study is justified. Our main findings are: (1)  The prevalence rate of painful TMD (16.2%) found in the present sample is in accordance with previous studies that have shown rates varying from 7.3% to 30.4% in adolescents 6 . The instrument used for the TMD assessment and the age of the sample can contribute to the variation observed across previous studies. We did not find significant differences regarding the presence of TMD pain between genders, or the pubertal developmental stages.
Previous studies have shown that painful TMD is associated with the presence of pain in other parts of the body. 26,27 Our findings agree with the literature confirming the association between painful TMD and regional and widespread pain. The association between painful TMD and the persistent regional pain can be related to the neural inputs from the superior There is a lack in the literature regarding the association between systemic diseases and TMD in adolescents. In adults, previous studies showed an association between the presence of TMD and some specific systemic diseases, such as irritable bowel syndrome, 32 heart diseases, 13 and autoimmune diseases, such as rheumatic disease. 15 In our sample, asthma and bronchitis were significantly associated with painful TMD. We highlight that although we found a significant association between respiratory conditions and the presence of painful TMD, the number of participants affected by both was small.
We found 18 adolescents with painful TMD reporting previous diagnosis (informed by their parents or legal guardians) of bronchitis, and eight reporting asthma.
Although our results should be interpreted with caution and confirmed in future studies, they are aligned with a previously conducted study, demonstrating BRAIDO GV, CAMPI LB, JORDANI PC, FERNANDES G J Appl Oral Sci. 2020;28:e20190608 8/10 a positive correlation between TMD and respiratory diseases in children. 33 The presence of some degree of inflammation in the respiratory system and in the organism overall seems to be associated with bronchitis and asthma. 34  Our study has some limitations. Firstly, since it was a cross-sectional study, causation cannot be inferred. We assessed the presence of systemic diseases through the report of the adolescent's parents or legal guardian, so no definitive diagnosis was provided, neither the severity of the diseases. Therefore, the gold standard diagnostic tool, which would be an accurate medical examination and assessment conducted within the last 12 months, 37 was not possible. However, the sample had an adequate size, as described in the results.
Another limitation was regarding the type of school. Most of the sample were enrolled in public schools, due to a low participation response of students from private schools, who did not return the consent form signed by their parents/legal guardians. Finally, it is important to point out that the presence of pain in adolescents is often associated with anxiety and depression symptoms. 8,9 Given this, future studies should address the interaction of these psychological factors with painful TMD, and the associated variables found in this study.
The study's strengths are related to instruments and sampling. Translated and validated instruments with easy interpretation for adolescents were applied to evaluate the conditions studied. For TMD classification we applied the RDC/TMD, and the researcher who