The long-awaited initial findings from the largest and most comprehensive prospective study to date of chronic pain are shedding light on the common condition of jaw pain. In eight papers in a special issue of The Journal of Pain, published November 10, researchers from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) collaboration present detailed data on potential risk factors for temporomandibular disorders (TMD), a collection of chronic pain conditions that involve restricted movement and popping and clicking in the temporomandibular joints of the jaw.
Uncovering risk factors for TMD (also known as temporomandibular joint and muscle disorders, TMJD) should help demystify diagnosis, illuminate biological mechanisms, and point to strategies for treatment. Samuel Dworkin, University of Washington, Seattle, writes in an accompanying editorial that “chronic TMD remains enigmatic” and calls the new project “the first-ever large, prospective clinical study to identify risk factors that contribute to someone developing and persisting with a TMD condition.” Researchers hope that the results will also translate to other types of chronic musculoskeletal pain.
Headed by William Maixner at the University of North Carolina at Chapel Hill (UNC) and funded by the National Institute of Dental and Craniofacial Research (NIDCR) of the U.S. National Institutes of Health, OPPERA brings together researchers and patients at four universities, along with the Data Coordinating Center at the Batelle Memorial Institute, Durham, North Carolina. A paper by Gary Slade, UNC, and collaborators in the current clutch of reports outlines the design of the project, which includes both baseline and prospective components. The conceptual model was first described in a 2006 paper (Diatchenko et al., 2006), and is discussed in this compendium in an overview by Maixner and others.
The results represent the first phase of the effort: a baseline case-control study of 185 people with chronic TMD and 1,633 healthy controls. Researchers studied subjects in unprecedented detail, gathering information on their clinical history, psychosocial characteristics, pain sensitivity, autonomic function, and genetic characteristics.
The baseline study showed that females were several times more likely than males to have TMD. Volunteers were 18 to 44 years old, and, in contrast to some previous findings, TMD risk increased with age within this range. Subjects classified as Non-Hispanic Whites were five times more likely than other groups to have TMD. TMD prevalence did not correlate with socioeconomic status.
Researchers ran subjects through 36 experimental pain tests, and found that people with TMD were significantly more sensitive in most of the tests, and showed heightened sensitivity to pain in parts of their bodies besides the face or head. Joel Greenspan, University of Maryland Dental School, Baltimore, and colleagues report that the largest differences were in pressure pain thresholds. Other data showed that TMD was also associated with changes in autonomic function; patients showed elevations in heart rate compared to healthy participants, for example.
Diverse psychosocial factors also affected the risk of pain. Roger Fillingim, University of Florida, Gainesville, and colleagues report that TMD was most strongly associated with somatic awareness (being bothered by physical sensations), along with affective distress (anxiety and mood) and pain catastrophizing.
Clinical evaluations showed numerous differences between patients and controls as well. Richard Ohrbach, University at Buffalo, New York, and colleagues report that people with TMD experienced more comorbid pain conditions and neural and sensory conditions, reported a greater history of injury, and had more non-pain symptoms in the facial area than did healthy controls.
Finally, Shad Smith and Luda Diatchenko, UNC, and colleagues evaluated single-nucleotide polymorphisms in 358 candidate pain genes. They confirmed existing associations for two genes, HTR2A and COMT, and revealed new potential risk factors in NR3C1, CAMK4, CHRM2, IFRD1, and GRK5.
The seven-year project was launched in 2005, so the work is far from finished. Ongoing studies are following subjects over time to capture disease onset and watch its course.
The authors stress that the preliminary findings represent putative risk factors for TMD. The questions remain whether the associations can predict a person’s chances of developing TMD, and if the condition can become chronic. Those are issues that the ongoing longitudinal study is poised to answer.
Watch PRF for more detailed coverage of the results and next steps in the OPPERA study.
Read press releases from participating institutions:
National Institute of Dental and Craniofacial Research; University at Buffalo; University of Florida; University of Maryland; and University of North Carolina.
