Investigators analyzing the data collected in the long-running clinical study Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) have now published their findings comparing individuals, all of whom were TMD free at the start of the study, with 260 individuals who developed first-onset TMD in the course of follow-up examinations. The papers, published as a special supplement to the December issue of the Journal of Pain (the official journal of the American Pain Society) indicate that a number of factors in many domains (e.g., genetic, environmental, physiological, psychological, behavioral) contribute to the development of TMD. It is important to note that no single risk factor in and of itself was found to be either necessary or sufficient to cause TMD, confirming what researchers have long acknowledged: TMD is a complex “multifactorial” disease. Note: Having one or another risk factor does not mean that an individual is destined to get TMD. Risk factors are not destiny.
That said, what did the researchers find? First, whom did they study? Between May 2006 and November 2008, investigators at four college campuses led by William Maixner and colleagues at the University of North Carolina, Chapel Hill, recruited 3,263 men and women volunteers ages 18 to 44. All those accepted for the study were TMD free and underwent physical examinations, filled out questionnaires, and had tissue samples collected at the outset, agreeing to follow up with periodic re-examinations and questionnaires. However, 16 percent of this initial group were “lost to follow-up” and because of missing or dubious data, the number of volunteers for whom repeated data was available was reduced to 2,737. The researchers acknowledge that analyzing data only for the reduced number could bias the study (meaning that analysis and interpretation of results would deviate from true findings) but using statistical methods they concluded that there was only a small, “though not ignorable, degree of bias.”
Given that the recruitment period for the study extended over two years, individuals who developed TMD might have had shorter or longer periods of follow up before the TMD diagnosis. The median follow-up time for the 260 men and women who developed disease was 2.8 years. The researchers calculated that this would yield an annual incidence rate (including those lost to follow-up) between 3.5 and 4 percent of the population.
The following is a summary of the factors that distinguished the group who developed TMD from those who remained disease free over the 5 years of the study period. The significance of this work is that for the first time it identifies in a large sample factors that may predispose an individual to TMD, characteristics actually involved in causing the disease. This is in contrast to case-control studies in which people (patients) who already have a disease are compared to a similar group of people who do not have the disease, looking for factors that differ between the groups. The problem here is that there is no way of knowing if any differences found in patients actually caused the disease or were a result of the disease process. (As an example, people with a chronic pain condition may experience depression compared to a control group, but did the depression help cause the disease or was it a consequence?) This month we report on the findings for two of the domains studied. Next month we will review the findings on sociodemographic and psychological factors and the following month on genetic and pain sensitivity and autonomic factors.
Clinical Orofacial Predictors
Analysis of baseline self-reported questionnaires and clinical examinations involving 41 different measures found only a few factors that were predictive of TMD onset. Based on clinical examinations, these included pain from jaw opening and pain from palpation (applying fixed levels of pressure) on masticatory, neck and body muscles. Neither joint noises, nor evidence of tooth wear predicted TMD onset. Information from questionnaires indicated that individuals who reported three or more non-specific orofacial characteristics such as jaw stiffness, cramping, fatigue, pressure, soreness and ache (but not pain) had twice the incidence of TMD compared to those who reported fewer than 3 such symptoms. First-onset TMD was also predicted by higher numbers and/or frequencies of what are called “parafunctional” behaviors such as chewing gum, holding the jaw rigid or clenched, and holding objects between the teeth. The investigators speculate that these behaviors reflect overactive motor nerve activation or underactive motor nerve inhibition at the level of the central nervous system - the brain and spinal cord.
General Health Status Predictors
A battery of questionnaires at the outset determined whether enrollees had one or more pain disorders - specifically, tension and migraine headaches, irritable bowel syndrome, genital symptoms and low back pain, how they assessed their general health status, what medical conditions they had now or in the past grouped in five categories: endocrine, cardiovascular, hematologic (blood) disorders, neural and sensory, and respiratory. They were asked whether they smoked, how they judged their quality of sleep and whether they had been hospitalized for serious surgery or illness. A number of these factors were chosen because of previous studies suggesting that chronic TMD overlaps with several other pain conditions and has associations with cigarette smoking and sleep disturbances. But again these past associations could not answer whether TMD gives rise to sleep disorders or vice versa, nor if other bodily pain conditions precede or follow a TMD diagnosis. Another test used photos of enrollees’ hands to compute the ratio of the length of the second digit to the fourth digit. A high ratio indicates greater exposure to estrogen relative to testosterone in utero.
The presence of any of the listed pain disorders was associated with greater TMD incidence and the more episodes or number of pain conditions, the greater the chances of developing TMD. Irritable bowel syndrome showed strong effects. Incidence of first-onset TMD was three times as high in people with IBS at enrollment compared to twice as high for people who reported low back pain at enrollment. Similarly, incidence of TMD was three times higher in the 84 people who had genital pain at the outset compared to enrollees without genital pain. Tension-type headache was more strongly associated with TMD incidence than other headache types.
Some specific health conditions not primarily painful in nature including respiratory and neurosensory conditions were also associated with TMD incidence. The global health self-appraisal and selected items on a 20-item checklist were also predictive. Among them were some pain conditions (including fibromyalgia) but also a tendency to faint, insomnia, and ringing in the ears. Preexisting pain conditions, poor sleep quality, cigarette smoking and a high digit ratio were all independently associated with TMD incidence. Investigators commented that the finding that a higher exposure of the fetus to estrogen in utero increases TMD incidence “poses the intriguing possibility of organizational hormonal contributions to TMD.”
By Joan Wilentz, TMJA
About OPPERA: In 2006 The National Institute of Dental and Craniofacial Research (NIDCR) announced the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA). OPPERA I was a seven-year, four-site pain clinical study. The $19.1 million project was the first-ever large, prospective clinical study to identify risk factors that contribute to someone developing TMJ Disorders. In 2012 the OPPERA investigators were awarded $16 million by NIDCR to continue their research for another five years under the OPPERA II. The second study is designed to build on the findings of OPPERA I and deepen the understanding of risk factors and genetic markers for chronic pain conditions like TMD, headaches, irritable bowel syndrome, low back pain and chronic widespread pain. OPPERA I and OPPERA II are critical to furthering our knowledge about human pain conditions. They allow us to identify biological, psychological and genetic contributions to common and frequently debilitating pain conditions. Once we better understand the causes of chronic pain and how one type of pain condition relates to another, we'll be better able to treat those who suffer daily from these disorders.