The National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health, announced today the launch of a seven-year clinical study that could accelerate research on better pain-controlling treatments for a jaw condition called temporomandibular joint and muscle disorders (TMJDs).

Called Orofacial Pain: Prospective Evaluation and Risk Assessment, or OPPERA, the $19.1 million project marks the first-ever large, prospective clinical study to identify risk factors that contribute to someone developing a TMJ disorder. A prospective study looks forward in time, tracking volunteers over several months or years to monitor the onset and natural course of a disease.

During the OPPERA study, scientists will track 3,200 healthy volunteers from three to five years to see how many develop the disorder. According to Dr. William Maixner, the study’s principal investigator and a scientist at the University of North Carolina in Chapel Hill, those who develop TMJ problems will open a critical and largely unexplored window on the early stages of the disorders, pointing the researchers toward genes and other biologic factors that might contribute to pain sensitivity.

Maixner said the high-quality data generated from this prospective vantage point could provide the future impetus to refine diagnostic criteria for TMJ disorders, consider new approaches to treatment, and predict a person’s natural susceptibility to develop a chronic pain condition. "This is a timely study that will greatly enhance the scientific underpinnings of research on TMJDs,” said NIDCR director Dr. Lawrence Tabak. “Most importantly, it will accelerate the pace of the science and seed valuable new leads that impact virtually every aspect of care for the disorders.”

"This study represents an important step forward not only for TMJD research but pain research in general," said NIH director Dr. Elias Zerhouni. "It marks one of the first - if not the first - prospective clinical studies to identify risk factors for a chronic pain condition. It's quite possible that some of the findings that arise from this study will be applicable to other musculoskeletal pain conditions."

TMJD is an umbrella term for a group of conditions that affect the area in and around the temporomandibular joint, or TMJ. These two large, ball-and-socket joints connect the jaw to the skull on both sides of the head, and common symptoms of a TMJ disorder include persistent pain in the jaw muscles, restricted jaw movement, jaw locking, and abnormal popping and clicking of the joint.

It is not known precisely how many people have TMJDs, but the main symptoms-pain and restricted jaw movement-occur in 5-15 percent of Americans. TMJ disorders may be more common in women than men and, while some conditions can be linked to physical trauma, in most cases the cause is unknown.

Although TMJ disorders vary in their duration and severity, for some people the pain becomes a permanent feature of their lives, and controlling it can be an exercise in frustration for them and their doctors. In the absence of generally accepted, science-based guidelines for managing TMJ disorders, health care providers have tried to help patients using a variety of approaches, often with unsatisfactory results.

One reason that relief is so difficult to find is the chronic pain associated with TMJ disorders results form a highly complex biological interplay. The interplay involves myriad factors, ranging from the intricacies of pain transmission and its possible rewiring and overamplification en route to the brain to the complicating and frequent presence of other painful conditions, such as fibromyalgia and chronic fatigue, which possibly mask or modify the symptoms of the TMJ problem.

With so many variables, some researchers have suggested that the best scientific entry point to examine a TMJ disorder is during its earliest stages, before the full-blown complexity of advanced disease clouds the investigative picture. This thinking and recent progress in studying the basic biology of pain led to the NIDCR’s decision to support the OPPERA study. The multi-center research program will involve investigative units at: University of Florida in Gainesville, directed by Dr. Roger Fillingim; University of Buffalo-SUNY, directed by Dr. Richard Ohrbach; University of Maryland at Baltimore, directed by Drs. Joel Greenspan and Ronald Dubner, and the University of North Carolina Chapel Hill, directed by Dr. William Maixner.

This study builds on the recent completion of a successful three-year, prospective pilot study in North Carolina that involved 240 healthy women who initially had no history of a TMJ disorder. In the OPPERA study, participants may be both male and female. All must be between the ages of 14 and 44, in good health, and have had no previous TMJ problems. Based on the results of the pilot study, Maixner said an estimated 200 volunteers may develop their first TMJ disorder during their participation in OPPERA.

“A large prospective study on a TMJ disorder would have been futile just a decade ago because not enough was known about the basic mechanisms that control human pain,” said Maixner. “It’s only been within the last few years that an adequate conceptual framework has emerged, and I’m very hopeful OPPERA will identify key genetic, physiologic, and psychological variables that tell us more about patients and, ultimately, lead to more effective treatment approaches.”

The National Institute of Dental and Craniofacial Research is the nation's leading funder of research on oral, dental, and craniofacial health.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.