1. Introduction

Temporomandibular disorders (TMD), specifically those associated with pain, are currently understood as a set of signs and symptoms that designate a painful musculoskeletal syndrome, often linked to multisystemic changes, including alterations in behavior, emotional status, and social interactions. These manifestations are recognized as expressions of central nervous system dysregulation. Among the main predictors for the development of painful TMD are the presence of comorbidities, self-reported parafunctions, the frequency of somatic symptoms, poor sleep quality, and genetic and epigenetic factors. It is important to note that self-reported parafunctions, while not classified as orofacial or somatic symptoms, represent behavioral factors that contribute to the risk of TMD. This study focuses on the painful subtype of TMD, which is of particular clinical relevance due to its impact on quality of life and its association with chronic pain mechanisms [1,2].

Painful TMD includes diagnoses such as myofascial pain, arthralgia, and headaches attributed to TMD, all of which are characterized by chronic orofacial pain and functional limitations. These painful subtypes differ from intra-articular TMD, which may present with joint noises or movement restrictions without significant painful discomfort. The specificity of diagnosing painful TMD is guided by the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD), which allows for the accurate identification of patients experiencing TMD for the last month. By focusing on painful TMD, this study seeks to investigate the cognitive-behavioral-emotional factors that contribute to the onset and persistence of pain in this specific population, differentiating it from the broader spectrum of TMD presentations [3].

The involvement of aspects with a cognitive-behavioral-emotional dimension in the manifestation of painful TMD has been increasingly studied, the identification of phenotypes at higher risk of developing the condition. The perception of TMD signs and symptoms is significantly modulated by emotional and social factors, which are associated with the multidimensionality of pain. Women with high levels of anxiety and stress are at higher risk of developing myofascial pain, and personal traits of anxiety, stress, catastrophizing, and hypervigilance are strongly associated with the diagnosis of painful TMD [4–6].

Pain sensitivity, including thresholds for allodynia and hyperalgesia, is significantly influenced by cognitive and emotional factors such as pain catastrophizing, anxiety, and stress, which modulate pain perception at both the sensory and central levels. Similarly, oral behaviors and pain vigilance are shaped by learned behavioral responses, driven by cognitive appraisals and emotional states such as fear of pain or hypervigilance. Central sensitization, often linked to physiological mechanisms exacerbated by emotional stress and cognitive distortions, further underscores the importance of including these variables in the cognitive-behavioral-emotional model of pain perception [7,8].

Identical (monozygotic) twins have always intrigued researchers since they present the same genotype at birth and develop, throughout life, differentiated phenotypes, becoming completely different individuals. In the last decade, several studies with discordant monozygotic twins have been published because, with this methodology, It is possible to establish a case-control study design in which several variables can be controlled, as they are shared between siblings, including genetic material, social environment (if raised in the same family), age, gender, and other factors [9,10].

The influence of the social environment on the development of chronic pain, combined with the presence of specific genetic polymorphisms, has been widely studied. The OPPERA study analyzed 300 genes that could be associated with the development of painful TMD; among these, six SNPs (single nucleotide polymorphisms) were identified as risk factors for chronic TMD, while six others were associated with intermediate phenotypes for painful TMD [2,11].

Few studies specifically addressing monozygotic twin populations have been conducted regarding painful TMD. These studies suggest a genetic component in the manifestation of the condition, evidenced by a higher degree of diagnostic concordance among monozygotic twins compared to dizygotic pairs. Furthermore, social interactions, individual behavioral patterns, and emotional factors play crucial roles in the development of chronic pain, contributing to phenotypes that warrant further investigation and understanding [12–15].

2. Objectives

Considering the literature presented, the primary objective of this case-control study was to investigate the cognitive-behavioral-emotional factors involved in the development of painful TMD. Variables such as pain sensitivity, oral behaviors, and central sensitization were selected due to their well-established roles in modulating pain through cognitive and emotional pathways. Accordingly, the study aimed to achieve the following specific objectives::

• To compare discordant MZ twins (each with their respective control) cognitive-behavioral-emotional variables.
• To compare groups of twins with painful TMD and control the cognitive-behavioral-emotional variables.
• To analyze cognitive-behavioral-emotional variables related to sociodemographic profile, pain sensitivity (pain threshold to pressure, allodynia, and hyperalgesia), oral behaviors, pain vigilance and awareness, pain catastrophizing, central sensitization, stress, anxiety, depression, alexithymia, mindfulness facets, sleep quality, pain control, pain intensity and interference, trigeminal and extra trigeminal pain areas.

3. Materials and method

4. Results

Table 1 shows the crude bivariate associations to explain the likelihood of TMD by analyzing the odds ratios (OR) and p-values. The variables that showed a positive association (according to the OR), however, without statistical significance, were pain duration, pain threshold to pressure (body, right side, upper trapezius/face, right, TMJ/ face, left, anterior temporal), pain sensitivity (body, right side, lateral epicondyle/face, right, anterior temporal/ face, right, masseter/face, left, anterior temporal/ face, left, masseter/face, left, TMJ), daytime oral behavior score, mean daytime oral behavior score, pain vigilance and awareness, pain catastrophizing (total/hopelessness), central sensitization (total score), stress, difficulty externalizing feelings, mindfulness facets (distraction/unresponsiveness), sleep quality (subjective sleep quality domain score/ overall score), pain intensity, and pain interference.

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Table 1. Crude bivariate associations to explain the likelihood of TMD. Variables with significant associations are highlighted with an asterisk. Sample size: 20 twins (10 pairs).

https://doi.org/10.1371/journal.pone.0320515.t001

Table 2 shows the multiple linear regression model adjusted including in the deterministic model the variables that had, in the bivariate exploration, p-value < 0.20 (Table 1) and that had, among themselves, Spearman’s linear correlation coefficient that was not statistically significant (p > 0.05), thus preventing the presence of multicollinearity in the final adjusted model.

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Table 2. Multiple logistic regression to explain the chance of TMD.

https://doi.org/10.1371/journal.pone.0320515.t002

In the unadjusted models, significant associations were observed between painful TMD and variables such as left-sided masseter face pain sensitivity (OR = 1.7, 95% CI: 1.2–2.6), total pain catastrophizing (OR = 2.5, 95% CI: 1.4–4.5), and difficulty in externalizing feelings (OR = 1.4, 95% CI: 1.1–2.1). However, these associations were attenuated after adjusting for confounding factors and no longer reached statistical significance. For example, the OR for left-sided masseter pain sensitivity decreased to 1.3 (95% CI: 0.9–2.1). This reduction suggests that while these factors may contribute to TMD risk, their independent effect is reduced when accounting for interrelated variables.

While the adjusted model did not identify statistically significant associations, variables such as increased pain sensitivity in the masseter muscle (OR = 3.29, 95% CI: 0.17–62.8, p = 0.428), higher levels of pain catastrophizing (OR = 1.08, 95% CI: 0.64–1.8, p = 0.776), difficulty in externalizing feelings (OR = 1.61, 95% CI: 0.13–2.9, p = 0.539), and higher scores on the distraction facet of mindfulness (OR = 4.65, 95% CI: 0.39–55.7, p = 0.225) were included due to their clinical relevance and their significant associations in the bivariate analysis (p < 0.20).

Table 3 summarizes the presence or absence of a TMD diagnosis based on the DC/TMD criteria. Notably, in all cases, twins diagnosed with TMD had at least one subtype classified as painful TMD.

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Table 3. Temporomandibular Disorders (TMD) diagnosis based on the DC/TMD criteria.

https://doi.org/10.1371/journal.pone.0320515.t003

5. Discussion

This study investigated the cognitive-behavioral-emotional variables associated with the development of painful TMD in a sample of monozygotic twins discordant for the condition. Our findings indicate that increased pain sensitivity in the masseter muscle, higher levels of pain catastrophizing, difficulty in externalizing feelings, and higher scores on the distraction facet of mindfulness were included in the final model due to their clinical relevance and their associations in the bivariate analysis (p < 0.20). Despite their lack of statistical significance in the adjusted model, these variables were selected to ensure a comprehensive exploration of cognitive-behavioral-emotional factors in painful TMD, particularly given their potential importance in clinical practice. The inclusion of these variables also reflects our effort to balance parsimony with the need to retain independent predictors while considering the limitations imposed by the sample size and the specificity of the study population. These results provide evidence that, even in genetically identical individuals, cognitive and emotional factors play a crucial role in the manifestation of chronic pain associated with TMD.

The attenuation of significance in the adjusted models is a well-recognized occurrence in multifactorial conditions like TMD, where multiple variables collectively contribute to disease risk. In our study, the adjusted logistic regression model accounted for potential confounding variables, which likely diluted the individual effects of pain sensitivity, catastrophizing, and emotional regulation. This does not negate the relevance of these factors but rather indicates that their isolated impact is less pronounced when analyzed alongside other interrelated predictors. This underscores the complexity of TMD, where psychological, emotional, and sensory factors interact dynamically to influence overall risk.

In comparison with previous studies, our findings support the notion that pain catastrophizing, a well-established psychological predictor of chronic pain, is significantly associated with TMD. For instance, research from the OPPERA study demonstrated that individuals with higher levels of catastrophizing were more likely to develop chronic TMD, aligning with our observation that this cognitive variable increases the likelihood of painful TMD [2]. However, our study adds to this body of knowledge by highlighting the specific roles of difficulty in externalizing feelings and the distraction facet of mindfulness, two variables that have been underexplored in previous TMD research. These emotional and attentional factors may serve as important targets for interventions designed to alleviate TMD-related pain.

According to the International Association for the Study of Pain (IASP), pain is defined as an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage. This comprehensive definition emphasizes the complex nature of pain, which integrates sensory, cognitive, and emotional dimensions [2]. Cognitive processes not only shape psychological outcomes, such as emotional regulation, but also directly modulate neural pathways involved in pain perception. The intricate interplay between cognition and pain underscores the need to assess these variables when investigating chronic pain conditions like TMD [18–20]. Consequently, examining cognitive-behavioral-emotional factors is essential for gaining deeper insights into the mechanisms underlying pain and for designing more effective, targeted interventions [19,20].

Including variables such as pain sensitivity and central sensitization in the cognitive-behavioral-emotional model is supported by evidence demonstrating the role of psychological factors, like catastrophizing and stress, in amplifying pain perception. These variables interact with cognitive appraisals and emotional responses, influencing pain intensity and chronicity. The findings of our study underscore the relevance of the biopsychosocial model in understanding chronic pain, particularly in the context of painful TMD. This model emphasizes the intricate interplay of cognitive, behavioral, and emotional factors in shaping an individual’s pain experience. Our results identified pain catastrophizing, difficulty in externalizing feelings, and the distraction facet of mindfulness as key predictors of painful TMD. These findings highlight the necessity of addressing emotional and cognitive dimensions alongside the physical aspects of pain in the management of chronic pain syndromes. Consistent with prior research, these factors play a pivotal role in how individuals perceive and respond to pain, and their accurate identification can significantly enhance treatment strategies and outcomes for patients [19–22].

In line with the findings from the OPPERA study, our research corroborates those psychological factors, particularly catastrophizing, are strongly associated with the development and persistence of painful TMD. The OPPERA study’s multivariable analysis identified global psychological and somatic symptoms as robust risk factors for TMD onset [23]. Similarly, in our study, catastrophizing emerged as a significant cognitive predictor, underscoring the impact of negative thought patterns in intensifying pain and disability. The well-established association between catastrophizing and increased pain intensity reinforces our conclusion that targeting this cognitive factor could play a crucial role in mitigating TMD symptoms.

Moreover, while the OPPERA study focused on broader psychosocial predictors such as stress and somatic symptoms, our study extends the understanding of TMD by identifying more nuanced emotional factors like difficulty externalizing feelings. This finding contributes to the growing evidence that emotional regulation and expression are critical factors in the chronicity of pain conditions. Individuals who struggle with emotional expression may internalize stress, thereby exacerbating their pain experience. This insight highlights a potential intervention pathway, emphasizing the development of emotional intelligence and communication skills as integral components of a holistic approach to managing TMD.

Our study also highlighted the role of mindfulness, particularly the distraction facet, in modulating the pain experience. Mindfulness-based interventions have gained increasing recognition as effective tools for managing chronic pain, including TMD [21]. The ability to redirect attention away from pain and maintain a neutral stance towards bodily sensations reduces the psychological burden of pain. By training individuals to dissociate from the emotional distress associated with pain, mindfulness can reduce the intensity of the pain experienced, as our findings suggest. The implications for therapeutic interventions are significant, as mindfulness training could be integrated into conventional pain management programs to enhance their effectiveness.

In contrast to studies that emphasize the heritability of chronic pain, such as the work by Burri et al. (2018), which found a vital genetic component in chronic pain conditions [15], our study underscores the critical role of environmental and psychological factors, even among monozygotic twins. While genetic predisposition undoubtedly plays a role, as highlighted by Burri’s findings, our results indicate that cognitive and emotional variables may supersede genetic factors in the manifestation of painful TMD. This has significant implications for personalized treatment approaches, suggesting that interventions focusing on cognitive-behavioral-emotional factors could be effective even in individuals with a genetic susceptibility to pain.

Epigenetics represents a key mechanism in understanding the complex interaction between genetic predisposition and environmental factors in the development of chronic pain conditions like TMD. Recent studies have shown that epigenetic modifications, such as DNA methylation and histone acetylation, can influence gene expression in pathways associated with pain sensitivity and inflammation, thereby modulating the risk of chronic pain syndromes [24,25]. By utilizing a monozygotic twin sample, our study minimized genetic variability, allowing us to focus on non-genetic influences, including potential epigenetic modifications. This approach is particularly valuable for exploring how environmental stressors and psychological factors, such as catastrophizing and emotional dysregulation, contribute to altered pain processing in TMD. Investigating epigenetic markers in this context could provide valuable insights into the biological underpinnings of TMD, as suggested by studies demonstrating the impact of epigenetic changes on central sensitization and chronic pain development [26,27].

The specificity of our sample, composed of monozygotic twins discordant for painful TMD, provides a unique advantage in examining the interaction between genetic, environmental, and psychological factors. This controlled design enables us to isolate the impact of cognitive-behavioral-emotional variables without the confounding effects of genetic differences. Additionally, the inclusion of a broad range of variables—spanning pain sensitivity, mindfulness facets, emotional expression, and central sensitization—allowed us to construct a comprehensive profile of factors contributing to painful TMD. This multifactorial approach aligns with contemporary research emphasizing the integration of psychological and biological dimensions for a holistic understanding of chronic pain syndromes [2,18,26–28]. The robustness of our model is further strengthened by the inclusion of key psychosocial factors, such as catastrophizing and emotional dysregulation, which are consistently associated with worse pain outcomes and resistance to treatment in chronic pain populations [20].

In genetically identical individuals, such as the monozygotic twins in our study, non-genetic factors- environmental, psychological, and epigenetic- emerge as particularly influential in the development of chronic pain conditions like TMD. Our findings reinforce that, even without genetic diversity, cognitive-behavioral-emotional factors such as pain catastrophizing, difficulty in emotional expression, and mindfulness play a pivotal role in pain perception and modulation. Studies have shown that environmental stressors and psychological variables can induce epigenetic changes, influencing gene expression and central sensitization mechanisms [26–28]. This underscores the notion that, in genetically identical populations, modifiable factors such as emotional regulation and cognitive patterns may exert a greater influence on pain outcomes than genetic predispositions alone. The ability to isolate these effects in monozygotic twins highlights the critical role of psychological and behavioral interventions, offering the potential for more targeted and effective treatments for chronic pain in individuals with shared genetic backgrounds.

Furthermore, our results align with the growing recognition of central sensitization as a critical mechanism in chronic pain, particularly in TMD [18,29]. Central sensitization, characterized by an amplified response to pain stimuli, is thought to be modulated by both sensory and cognitive-emotional factors. In this context, our findings on pain catastrophizing and mindfulness distraction are particularly relevant, as both these factors are known to influence central pain processing [29–31]. This reinforces the idea that cognitive and emotional interventions may not only reduce the subjective experience of pain but also address underlying neurobiological mechanisms involved in TMD.

It is important to note that while our study adds to understanding the role of cognitive-behavioral-emotional factors in painful TMD, it also highlights areas for future research. Larger and more diverse samples are needed to validate these findings further and explore the potential for integrating mindfulness and emotional regulation techniques into standard treatment protocols for TMD. Furthermore, future studies could investigate how these factors interact with biological markers such as inflammatory and oxidative stress responses to provide a more comprehensive picture of the pathophysiology of TMD. Moreover, although the age criterion (18–55 years) was implemented to minimize confounding factors related to age-associated changes in pain perception, comorbidities, and cognitive-emotional responses, this restriction also represents a limitation in this study, as age could have been considered a potential confounder in the analysis, allowing for a broader understanding of its influence.

Our findings underscore the importance of a multifaceted approach to the treatment and management of painful TMD, addressing not only the physical manifestations of the disorder but also the psychological and emotional factors that contribute to its chronicity. Integrating interventions such as emotional intelligence training, mindfulness practices, and cognitive-behavioral therapies holds significant promise in improving patient outcomes by targeting both pain’s sensory and affective dimensions. Future research should focus on evaluating the efficacy of these interventions through clinical trials and exploring the potential interaction between cognitive-behavioral-emotional factors and biological markers, such as inflammatory and oxidative stress responses. A deeper understanding of these interactions could pave the way for developing personalized treatment protocols aimed at effectively reducing pain and enhancing the quality of life for individuals with TMD. Future research would benefit from employing advanced statistical techniques, such as interaction or mediation analysis, to unravel the dynamic relationships between cognitive-behavioral-emotional factors and TMD development. Such approaches could provide more nuanced insights into how these factors influence disease outcomes, enabling more targeted interventions.

6. Conclusions

Our study investigated cognitive-behavioral-emotional factors potentially associated with painful TMD in a unique sample of monozygotic twins discordant for the condition. While the adjusted model did not identify statistically significant associations, variables such as increased pain sensitivity in the masseter muscle, higher levels of pain catastrophizing, difficulty in externalizing feelings, and higher scores on the distraction facet of mindfulness were included due to their clinical relevance and their significant associations in the bivariate analysis. These findings contribute to understanding the potential role of these variables in painful TMD, highlighting their relevance for clinical practice and the need for further exploration. Our approach emphasizes the importance of balancing parsimony and clinical applicability, while recognizing the limitations of sample size and study specificity. Future studies with larger populations are essential to confirm these results and to further investigate the interplay between cognitive-behavioral-emotional factors and painful TMD.