The Prevalence of Comorbid Symptoms of Central Sensitization Syndrome Among Three Different Groups of Temporomandibular Disorder Patients

Recently, there has been a substantial amount of interest directed at investigating temporomandibular disorder (TMD)1. The motivation to better understand this pain condition was stimulated by many studies demonstrating the apparent overlap of physical symptoms among TMD and other comorbid disorders, such as fibromyalgia (FM), chronic fatigue syndrome (CFS), and chronic headaches, etc 2. Symptoms involving aches and pains in the muscles and joints, cognitive problems, gastrointestinal disturbances, and changes in the quantity or quality of sleep are commonly observed among those with TMD, FM, and CFS. Indeed, 75% of those with FM can also be diagnosed with TMD using the Research Diagnostic Criteria for TMD (RDC/TMD), whereas 35% to 70% of those with CFS meet the criteria for FM3. Yunus4 discusses the implications of the terms that have been used to classify these disorders. He explains that, traditionally, the polysymptomatic patient would have been given a “wastebasket” diagnosis, such as “somatoform disorder,” or “multiple symptoms disorder.” Such terms potentially complicate patient-physician relationships as they imply, at some level, that the symptoms are purely psychological, and, therefore, “not real.” Moreover, as the etiology is poorly understood, such phenomenology possesses certain connotations that are not conducive to effective treatment strategies. With more research demonstrating the possibility that these disorders could result from similar underlying mechanisms involving central sensitization (CS), the term central sensitization syndrome (CSS) has been introduced in an attempt to provide more validity in searching for some underlying etiology than was previously offered by terms used in the past4. Although there is yet no conclusive evidence that CS is a common etiological factor of TMD and comorbid CSS, several studies have made a convincing argument in favor of such an etiology5. In many cases, CS is the basis of chronic pain, “or pain that persists beyond a normal time of healing”6. It is characterized by hyperexcitability in the dorsal horn neurons in the spinal cord, which ascend through the spino-thalamic tract7. In addition, it is promoted and maintained by neural activity among key regions in the brain involved in pain processing. The general assumption is that the central nervous system is altered in ways that amplify pain processing. Consistent with the idea that CS may be involved in the pathogenesis of TMD, the Orofacial Pain: Prospective Evaluation of Risk-Assessment (OPPERA) study was funded to investigate the biopsychosocial factors of TMD8. The general hope among the collaborators was that important risk factors or mechanisms would be elucidated, which might provide some insight for other musculoskeletal pain conditions. Among the studies, Greenspan and colleagues9 identified increased pain sensitivity to different types of experimental pain at multiple body sites beyond the orofacial region. Genetic risk-factors were also identified among those with TMD, which have demonstrated to be important in pain transmission10. Specifically, they found that polymorphisms on the genes, that encode for dopamine and serotonin, were positively correlated with pain severity, suggesting a genetic basis for the hypersensitivity experienced among those with TMD. Moreover, the dysregulation among neuroendocrine and neurotransmitter systems observed within the TMD population is highly related to the dysregulation of the hypothalamic pituitary adrenal (HPA) axis10. Dysfunction of the HPA axis has been consistently demonstrated to be involved in TMD and other comorbid pain conditions11. The HPA axis serves as an important intermediary among neuroendocrine, neurotransmitter, and neuroimmune systems, all of which have been suggested to be imbalanced among those with TMD and CSS. In fact, Maixner and colleagues12 identified altered function among those with TMD at rest, and in response to physical and psychosocial stressors. Specifically, they investigated indirect measures of HPA axis function, including heart rate, heart rate variability, baroflex sensitivity, and blood pressure. Ohrbach and McCall 13 also proposed that prolonged stress exposure plays a more direct role in TMD pathogenesis, causing sustained increases in stress hormones that promote tonic muscle contraction and consequential orofacial pain. However, many others have suggested that emotional distress is a consequence of pain, while the majority support a view involving dynamic interactions among these factors14-15. The indirect influence of emotional distress can be observed in pain behaviors and cognitions common among these patients15-16. For example, it is typical for individuals to seek treatment when they experience pain. However, there is a sub-population of individuals who do not respond adaptively in this regard. The somatic amplification hypothesis suggests that some individuals become hypersensitive and hyperreactive to pain, benign somatic sensations, and stressful events16. Hyperreactivity often manifests itself in a highly catastrophic manner owing to the common tendency for these individuals to misinterpret their symptoms as indicators of serious illness when, in fact, there is none 16. For this reason, treatment-seeking is more common among those with CSSs, although these individuals are usually resistant to reassurance from physicians. A common concern among these individuals is that something important has been overlooked. In trying to convince physicians that there is “something wrong,” they reinforce their invalid beliefs that they have a serious medical disease that, in turn, engenders more emotional distress16. The influence of daily stressors is reflected in increases in the prevalence of somatic complaints, as well as the severity of symptoms during times of greater psychosocial stress (e.g., work load, interpersonal problems) 18-19. Subsequent increases in stress hormones and inflammatory factors in response to prolonged stress exposure has been linked to illness behavior, including changes in diet and exercise habits, activity level, and other maladaptive coping strategies that pose challenges for treatment 20. Also, studies have shown that having a muscle disorder and elevation on the Minnesota Multiphasic Personality Inventory (MMPI) Scale-2, which is considered a good indicator of psychosocial function, was predictive of poor treatment outcomes 20. More recent studies have demonstrated a pattern of elevation on the MMPI-2 (known as the “Disability Profile”) to be particularly problematic and resistant to treatment responsiveness 21. While the relationship between TMD and symptoms of CSS is becoming readily established, there still remains the need to identify what accounts for this relationship2. The current study was therefore designed to investigate the prevalence of comorbid symptoms across the various groups of TMD disorders (i.e., Axis I RDC/TMD Group I Muscle Disorders, Group II Disc Displacements, and Group III Bone Deficiencies). The importance of investigating the influence of emotional distress with respect to these disorders stems from the clinical observation that TMD and CSS are related4. Moreover, emotional distress is thought to play both a direct and indirect role in these disorders through the physiological mechanisms previously discussed, and through its ability to exacerbate the condition and hinder pain rehabilitation and management. Thus, the current study examines the contribution of emotional distress on the prevalence of comorbid symptoms of CSS, as well as in self-report of pain and pain-related disability. On the basis of previous research demonstrating indices of CS among those with TMD Muscle Disorders, it was predicted that those with an RDC/TMD Group I Muscle Disorder, and those with more than one diagnosis, would have more comorbid symptoms of CSS, as well as higher reports of pain and pain-related disability22. Additionally, it was expected that emotional distress would account for a significant amount of variance of symptoms of CSS, pain, and pain-related disability. Furthermore, it was predicted that all group comparisons would be mediated by emotional distress23.