Orthognathic treatment and temporomandibular disorders: A systematic review. Part 1. A new quality-assessment technique and analysis of study characteristics and classifications Authors' conclusions: The diversity of diagnostic criteria and classification methods used in the included studies makes interstudy comparisons difficult. There is a definitive need for well-designed studies with standardized diagnostic criteria and classification methods for TMD.

Orthognathic treatment and temporomandibular disorders: A systematic review. Part 2. Signs and symptoms and meta-analyses Authors' conclusions: Although orthognathic surgery should not be advocated solely for treating TMD, patients having orthognathic treatment for correction of their dentofacial deformities and who are also suffering from TMD appear more likely to see improvement in their signs and symptoms than deterioration.

Arthrocentesis and lavage for treating temporomandibular joint disorders. Authors' conclusions: There is insufficient, consistent evidence to either support or refute the use of arthrocentesis and lavage for treating patients with temporomandibular joint disorders. Further high quality RCTs of arthrocentesis need to be conducted before firm conclusions with regard to its effectiveness can be drawn.

Bone Graft Grown in Exact Shape of Complex Skull-Jaw Joint.

Cyclobenzaprine (Flexeril) for the treatment of myofascial pain in adults.

Treatment of Closed Lock of the TMJ. Surgery has long been the treatment of choice, since it was assumed that this was the only way to get the disk back in place. However, it was also known that symptoms can improve with simple symptom management, or a combination of symptom management and physical therapy. This prompted a group at the University of Minnesota to carry out a randomized clinical trial of four treatments for Closed Lock.

The methodological quality of systematic reviews comparing temporomandibular joint disorder surgical and non-surgicaltreatment. BMC Oral Health 2008, 8:27

Cyclobenzaprine for the treatment of myofascial pain in adults. There was insufficient evidence to support the use of cyclobenzaprine in the treatment of myofascial pain (MP). Further studies are needed to show whether cyclobenzaprine really works for treatment MP, but at the moment doctors cannot say whether it is really useful. Cochrane Database of Systematic Reviews.

Inconsistent evidence for the use of tricyclic antidepressants in the treatment of temporomandibular joint disorders. There is evidence, based on inconsistent or limited-quality patient-oriented data (SORT level B recommendation), for the use of tricyclic antidepressants (TCA) in the treatment of temporomandibular joint disorders (TMD).Evidence-Based Dentistry.

The effects of cycling levels of 17-estradiol and progesterone on the magnitude of temporomandibular joint (TMJ)-induced nociception. Hormone levels in female rats can affect the perception of pain in the temporomandibular joint (TMJ), providing a possible explanation for the higher incidence of TMJ pain in females, according to a study published online April 9 in Endocrinology.

Botulinum toxin for masseter hypertrophy:. Although the use of botulinum toxin injections might appear to have certain advanctages over surgery the authors in this review did not find any high quality studies evaluating the effectiveness and potential harms of botulinum toxin type A in the management of benign maseter hypertrophy.

The methodological quality of systematic reviews comparing temporomandibular joint disorder surgical and non-surgical treatment. The results indicate that in spite of the widespread impact of TMJD, and the multitude of potential interventions, clinicians have expended sparse attention to systematically implementing clinical trial methodology that would improve validity and reliability of outcome measures. With some 20 years of knowledge of evidence-based healthcare, the meager attention to these issues begins to raise ethical issues about TMJD trial conduct and clinical care.

In September 2007 the National Institute of Dental and Craniofacial Research convened a group of thought leaders to determine the best approaches for future basic and clinical research on TMJD within an integrated systems approach and various options to advance this goal. Click here to read the Final Report of the TMJD Working Group.

Occlusal splints for treating sleep bruxism (tooth grinding). This study found insufficient evidence to either support or refute the use of occlusal splints for treating patients with tooth grinding or clenching during sleep (sleep bruxism) Sleep bruxism is characterised by several signs and symptoms. Among them abnormal tooth wear, fractured teeth, joint pain or tenderness, jaw muscle discomfort, and headaches. Treatments include odontological devices such as occlusal splints, pharmacotherapy, and psychotherapy. An occlusal splint is a removable appliance worn in the upper jaw (maxilla) or the lower jaw (mandible), with coverage of the dental surfaces. They are usually used to prevent tooth wear. There is not enough evidence in the literature to show that occlusal splints can reduce sleep bruxism.

TMJD patients often experience tinnitus – ringing in the ears. The following articles in ScienceDaily indicate tinnitus could be caused by the brain. Researchers Find Sites In Brain Responsible For Tinnitus; Work Raises Possibility Of Treatments, Cure and Searching For The Brain Center Responsible For Tinnitus.

Cartilage engineered with human embryonic stem cells, 9/13/2007, By Eugene J. Koay, Gwen M.B. Hoben, Kyriacos A. Athanasiou

Rice University researchers have engineered musculoskeletal cartilages with human embryonic stem cells (hESCs), with the hope of eventually using the hESC-derived neotissue for the replacement of damaged or diseased cartilages, such as the temporomandibular joint (TMJ) disc, in humans.

The need for cartilage replacements results from the inability of human musculoskeletal cartilages to effectively heal. This can lead to functionally deficient tissue and can result in the clinical syndrome known as arthritis, a major clinical problem with significant social and economic burdens.

Though important progress has been made in recent years toward engineering replacement cartilages in the laboratory, there are still many challenges to address, including the identification of a useful source of cells that can generate the new cartilage. Cartilage tissue engineering requires many cells to produce a piece of tissue that has clinically relevant dimensions, and this requirement far exceeds our current capability to obtain cartilage cells from an individual patient.

Stem cells, from both embryonic and adult sources, may address this particular hurdle, though a great deal of work still needs to be performed. Human embryonic stem cells (hESCs), in particular, have been scarcely studied to date for cartilage applications.

Toward understanding the use of hESCs for generating cartilage, two questions need to be addressed. First, how can the cells be “differentiated” or coaxed into cartilage-producing cells? Second, how can the cells be used for tissue engineering of cartilage?

In a recent study published in the journal Stem Cells, the Rice University researchers, including myself, Ms. Gwen M.B. Hoben, and Professor Kyriacos A. Athanasiou, used National Institutes of Health (NIH)-approved hESCs which were differentiated in conditions with distinct regimens of biochemical agents (growth factors) that are known to have cartilage-inducing properties. The resulting cells were then used in a tissue engineering strategy called self-assembly, which deviates from traditional engineering approaches in that self-assembly does not require any scaffold material to direct the formation of tissue.

This self-assembly approach with the hESC-derived cartilage cells resulted in uniform pieces of cartilage with cellular, biochemical, and biomechanical properties most similar to the TMJ disc and the knee meniscus, which are both fibrocartilages. Interestingly, the cartilages from each distinct biochemical regimen had a unique set of characteristics, suggesting that different types of cartilage can be generated with a single cell source in hESCs.

This study was the first demonstration of the ability of cartilage-differentiated hESCs to “self-assemble” and produce such robust cartilage, though there is still room for improvement. Additionally, the concept of producing multiple types of cartilage with this single cell source is new for the field, as the different cartilages of interest have diverse structures and biomechanical functions.

This initial study sets the ground for new research that seeks to enhance the properties of the hESC-derived cartilage, direct their differentiation for specific cartilage applications, and determine the clinical applicability of these cells, including their safety. This work was funded by an unrestricted fund from Rice University.

Researchers at the University of North Carolina at Chapel Hill have discovered that commonly occurring variations of a gene trigger a domino effect in chronic pain disorders. The finding might lead to more effective treatments for temporomandibular joint disorder (TMJD) and other chronic pain conditions.

Catechol-O-methyltransferase (COMT), an enzyme that metabolizes neurotransmitters such as epinephrine, norepinephrine and dopamine and that has been implicated in the modulation of persistent pain, as well as cognition and mood, is regulated by a gene, also called COMT. Previous UNC-led research showed that common genetic variants of this gene are associated with increased pain sensitivity and the likelihood of developing TMJD.

Now, the researchers have discovered that specific variants of the COMT gene can dramatically affect the secondary structure of corresponding messenger RNA - which, in turn, leads to alterations in the amount of enzyme crucial for regulating pain processing. The discovery is published in the Dec. 22 issue of Science.

"TMJD is a complex pain condition that is frequently associated with other pain conditions such as fibromyalgia syndrome, chronic headaches and irritable bowel syndrome," said Dr. William Maixner, director of the Center for Neurosensory Disorders in UNC's School of Dentistry and a study co-author.

"This study has identified a new genetic mechanism that influences an individual's susceptibility to develop chronic pain conditions such as TMJD," Maixner said.

The study was conducted to understand the mechanism by which the identified genetic variants influence enzymatic activity and, ultimately, biological functions such as pain transmission. The researchers found that three major variants of COMT show significant differences in how they code for the secondary structure of messenger RNA, or mRNA. The differences lead to dramatic alterations in protein expression, which substantially influences pain sensitivity in humans.

These findings are clinically important because pain conditions resulting from low COMT activity or elevated catecholamine levels are likely to be susceptible to treatment with pharmacological agents that block beta 2- and beta 3-adrenergic receptors, which mediate COMT-dependent pain signaling, or that control mRNA secondary structure.

"Elucidating the genetic mechanisms that mediate pain perception will provide new insights into how chronic pain develops and will ultimately contribute to the identification of unique markers for diagnosing clinical pain conditions, as well as provide novel targets for the development of effective individualized therapeutics for TMJD and related conditions," said Dr. Andrea Nackley Neely, a research assistant professor in the Center for Neurosensory Disorders and the study's lead author.

"These data have broad medical and evolutionary implications regarding the analysis of variants common in the human population," Nackley Neely said. "It is believed that variants leading to altered protein structure have the strongest impact on gene function. However, this study demonstrates that combinations of common genetic variants that influence mRNA secondary structure may have even stronger effects and, thus, represent another key factor responsible for disease onset and progression."

"This study provides additional evidence of a genetic, molecular and physiological basis for pain perception and human pain conditions and should help to remove the stigma associated with conditions such as TMJD and fibromyalgia," said Dr. Luda Diatchenko, an associate professor in the center and the study's chief investigator.

Other researchers were Dr. Inna Tchivileva, a postdoctoral research associate within the Center for Neurosensory Disorders; Kathryn Satterfield, a former research assistant within the center; Dr. Olex Korchynskyi, a former postdoctoral research associate within the UNC-Chapel Hill School of Medicine's Thurston Arthritis Research Center; Dr. Sergei S. Makarov, a former associate professor at the Center for Neurosensory Disorders and the Thurston center and now president and chief executive officer of Attagene Inc.; and Dr. Svetlana A. Shabalina, a staff scientist with the National Center for Biotechnology Information.

Funding was provided by the National Institute of Dental and Craniofacial Research, National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke, all components of the National Institutes of Health. Additional support came from the Intramural Research Program of the National Center for Biotechnology Information.

Other Center for Neurosensory Disorders research initiatives are currently under way that further explore the genetic basis of pain: One seven-study, a $19-million National Institute of Dental and Craniofacial Research-funded agreement involving multiple institutions and based at the center, will follow 3,200 health individuals and 200 who have facial pain. Titled OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment), the study is designed to identify both environmental and genetic factors that increase an individual's susceptibility to TMJD and other chronic pain conditions.

Related link on OPPERA study: http://www.unc.edu/news/archives/dec05/maixst120505.htm

Note: Contact Dr. Nackley Neely at (919) 452-6588 (cell) and Dr. Diatchenko at (919) 672-4542 (cell)

The Fourth Scientific Meeting of The TMJ Association, A Systems Approach to the Understanding of TMJ as a Complex Disease, set as a top priority the goal of finding and studying the poorly understood relationship between TMJ and other medical conditions. The meeting took place in September in Bethesda, Md., at the Federation of American Societies for Experimental Biology.

Temporomandibular joint diseases and disorders, commonly called TMJ, are a collection of conditions characterized by jaw and facial pain and limitations in jaw movements. Injury and conditions that routinely affect other joints in the body, such as arthritis, may affect the temporomandibular joint.

The National Institute of Dental and Craniofacial Research of the National Institutes of Health estimates that more than 10 million people in the United States suffer from TMJ problems at any given time. While both men and women experience TMJ problems, 90 percent of the most severely affected are women in their childbearing years.

People diagnosed with TMJ may be experiencing other symptoms and medical conditions as part of broader multi-systems illnesses that go unrecognized. Patients with TMJ are most often diagnosed and treated primarily by dentists or oral surgeons, while another medical professional may be treating them for other conditions, such as allergies, headaches, fibromyalgia, cardiac arrhythmias, sleep disorders, movement disorders, tinnitus and irritable bowel syndrome, each treating one of the constellation of conditions without considering the body as a collection of interrelated systems.

"Patients often face bewildering, expensive and unproven treatments that may not help them because the connection between the conditions is not realized," says Terrie Cowley, president and co-founder of the TMJ Association, based in Milwaukee, Wis. "Making the connection between TMJ and these other illnesses could bring better understanding and, as a result, the hope for safer, more effective treatments."

Presenters at The Fourth Scientific Meeting of the TMJ Association included medical and dental clinicians, as well as basic scientists from many disciplines. The top recommendation from the September meeting was to direct the National Institutes of Health to create regional research centers for the study of TMJ disorders and other health conditions by focusing more closely on patients' full set of symptoms, including the "co-morbid conditions" so many TMJ patients exhibit.

The centers should work closely with universities and other agencies to develop basic research projects, while advancing clinical practices for better patient care along with stronger community medical and dental programs and education. Research should include many diverse fields such as endocrinology, neurology, immunology, rheumatology, epidemiology, bioinformatics, genetics and others.

This approach signals a paradigm shift in how TMJ diseases and disorders are studied and treated. Temporomandibular diseases and disorders are complex conditions that may be related to larger health issues that are influenced by genes, gender, environmental triggers, such as trauma, and behavior, the conference concluded.

"It is more important than ever that we understand the full scope of these disorders," said Dr. Allen W. Cowley, Jr., Chair and Professor of Physiology at the Medical College of Wisconsin, Chairman of the Scientific Meeting Planning Committee and husband of Ms. Cowley, the association's president and co-founder.

"For years we have heard many patients say their problems are not well understood and the treatments are not working." Ms. Cowley says. "People who are suffering need help and that's not always possible if their illness is not completely understood." "This conference brings us closer to better understanding why, so we can establish a standard of care for people who are experiencing what we currently call TMJ."

National Institutes of Health Co-Sponsors of The Fourth Scientific Meeting

• Office of Research on Women's Health
• National Institutes of Dental and Craniofacial Research
• National Institute of Arthritis and Musculoskeletal and Skin Diseases
• National Institute on Deafness and Other Communication Disorders
• National Institute on Drug Abuse
• National Institute of Neurological Disorders and Stroke

The TMJ Association's scientific meetings and continuous advocacy for multidisciplinary research have resulted in initiatives from the member agencies of the National Institutes of Health that will lead to multi-disciplinary research specifically focused on TMJ diseases and disorders.

A study, published in the Journal of Neurochemistry, identifies a key interaction between head and neck nerve cell proteins that may help shed light on migraines and temporomandibular joint disorders.

Researchers at Oregon Health & Science University's School of Dentistry have uncovered an interaction between two proteins in the nerve cells that carry pain information from the head and neck to the brain. The finding could play a significant role in the development of therapies to cure migraines and other craniofacial pain conditions like TMJ (temporomandibular joint) disorder. According to the National Institutes of Health (NIH), approximately 10 percent of Americans suffer from chronic pain conditions and a significant portion of them have chronic craniofacial pain.

"Our discovery reveals the complexities of pain signaling mechanisms from the head and neck to the brain," said Agnieszka Balkowiec, M.D., Ph.D., principal investigator, OHSU School of Dentistry assistant professor of integrative biosciences and OHSU School of Medicine adjunct assistant professor of physiology and pharmacology.

Head pain is signaled to the brain by what's known as the trigeminal nerve. The trigeminal nerve also conveys other types of sensation, such as touch and temperature, from numerous structures of the face, including skin, ears, cornea, temporomandibular joints and teeth. Studies suggest that the trigeminal nerve provides the signaling pathway for pain associated with migraines, TMJ disorder, periodontal pain, dental surgical pain, trigeminal neuralgia, head and neck cancer pain, and other neuropathic and inflammatory pain conditions.

The OHSU study focused on two trigeminal nerve cell proteins: Calcitonin Gene-Related Peptide (CGRP), and Brain-Derived Neurotrophic Factor (BDNF). Previous studies found that during a migraine attack, the stimulation of trigeminal nerve cells releases CGRP at the peripheral end of the cells, widening blood vessels in the brain coverings called meninges. Widening the blood vessels increases the flow of blood through the meninges and initiates an inflammatory process that likely contributes to the pain experience. Recent clinical studies show that blocking CGRP helps alleviate migraine pain.The discovery by Balkowiec and her team points to BDNF being a likely culprit behind head pain - a previously unknown finding. The OHSU team found that the stimulation of trigeminal nerve cells, as experienced during a migraine attack, leads to release of not only CGRP, but also BDNF. The study also found that BDNF is released by CGRP when trigeminal nerve cells are not stimulated. In fact, said Balkowiec, CGRP's role at the central end of the trigeminal nerve cells is likely to be the facilitation of BDNF release. BDNF has previously been shown to play an important role in pain signaling from other parts of the body, but this is the first time it has been considered to be a factor in head pain.

"What we now need to better understand is how the interaction between CGRP and BDNF affects pain signaling to the brain in various disorders," said Balkowiec.

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Balkowiec's team included School of Medicine doctoral student Ilya Buldyrev; School of Dentistry dental students Nathan Tanner and Loi Nguyen; School of Dentistry research assistant Hui-ya Hsieh; and Oberlin College senior Emily Dodd.

The research at OHSU was funded by grants from the National Institutes of Health, Medical Research Foundation of Oregon, American Association for Dental Research and the OHSU School of Dentistry.

Tinnitus is a sound in one or both ears or in the head when no external sound is present. It is often referred to as "ringing in the ears," although some people hear hissing, roaring, whistling, chirping, or clicking.

The National Institute on Deafness and Other Communication Disorders of the National Institutes of Health hosted a workshop on tinnitus December 5-6, 2005. The purpose of the workshop was to advise the National Institute on Deafness and Other Communication Disorders about research and training opportunities in the area of tinnitus. Linda Parkin, a TMJ patient who also experiences tinnitus, as do many TMJ patients, participated in the meeting. Click here to read the meeting summary.

The Cochrane Oral Health Group reveals common treatments for TMJ pain have not yet been proven to be effective, despite their popularity.

This study reported that "there is insufficient evidence to either support or refute the use of injection of substances such as hyaluronate into the joint." Although this substance is sometimes used to treat osteoarthritis in the knees or hips, there is not enough evidence to judge whether it is helpful for people with TMD. Even if the patient has osteoarthritis in other joints, it is still open to question as to whether this is the same disease process that affects the TM joints. Shi Z, Guo C, Awad M. 2005. Click here to view abstract.

This study found "no strong evidence of benefit from occlusal adjustment (adjusting the teeth's biting surfaces) for problems associated with the TM joint." Specifically, the review reported there is "no evidence from trials to show that (bite) adjustment can prevent or relieve temporomandibular disorders." Koh H, Robinson PG. 2005. Click here to view abstract.

The study results state "there is insufficient evidence to either support or refute the use of occlusal splints for treating patients with tooth grinding or clenching during sleep (sleep bruxism) Macedo CR, Silva AB, Machado MA, Saconato H, Prado GF. 2007. Click here to view abstract.

This study concluded "there is insufficient evidence either for or against the use of stabilisation splint therapy for the treatment of temporomandibular pain dysfunction syndrome." Al-Ani MZ, Davies SJ, Gray RJM, Sloan P, Glenny AM. 2005. Click here to view abstract.

This study found "insufficient evidence to draw any conclusions about the effectiveness of transcutaneous electrical nerve stimulation (TENS) for the treatment of chronic pain in adults." D Carroll, RA Moore, HJ McQuay, F Fairman, M Tramer, G Leijon. 2005. Click here to view abstract.

(The Cochrane Collaboration is an international organization that aims to help people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of healthcare interventions. The main work of the Collaboration is done by approximately fifty Collaborative Review Groups, within which Cochrane Systematic Reviews are prepared and maintained. The Cochrane Oral Health Group aims to produce systematic reviews which primarily include all randomized control trials (RCTs) of oral health. Oral health is broadly conceived to include the prevention, treatment and rehabilitation of oral, dental and craniofacial diseases and disorders.)

viewTMJ Science.

As evidenced by recent work on TMJ tissue engineering, there is hope that the difficult problem of regeneration of tissues related to the TMJ may become tractable in the near future. Dr. Kyriacos Anthansiou's group at Rice University in Houston Texas has contributed a short article to the TMJA describing efforts pertaining to tissue engineering the disc of the TMJ. This article explains the basic premise of tissue engineering, which is essentially to create a new tissue in the laboratory to replace damaged tissues that cannot heal on their own. In more serious cases of disc displacement, which usually involve locking of the jaw and pain, the disc becomes so damaged that it cannot be repaired or repositioned with surgery. As a fibrous cartilage, it cannot heal, and therefore we are using tissue engineering as a strategy to replace the disc. The article describes some fundamental properties of the TMJ disc that distinguish it from the types of cartilage found in the knee or in the ear, for example. The type of patients who would be potential candidates are described, as are cutting-edge strategies to generate a healthy, new TMJ disc with the burgeoning science of tissue engineering. The article concludes with a look to the future for this exciting and promising new approach. The aim of this review article is to suggest that rational approaches are now implemented with the ultimate aim being the engineering of the TMJ disc.

Another strategy to tackle the difficult problems associated with TMJ disorders is to use tissue engineering to replace the condyle, or tip, of the jaw bone in the TMJ. It is exactly this that Jeremy Mao is striving to achieve. His teams approach is to replace both the bone and the cartilage on its surface. In recently reported work, they gathered cells from the bone marrow of rats, then exposed them to different environments to encourage them to become either cartilage cells or bone cells. These cells went into separate liquid solutions that were then hardened into the shape of a human condyle by using UV light. Each construct was then implanted under the skin on the back of a mouse for a few months. This creative approach has produced encouraging results, creating regions containing elements characteristic of bone and cartilage. There is much work to do before patients will see a resulting product, as these engineered constructs will still need to be validated for mechanical integrity. However, his group has emerged as a leader in the field and the potential of their work is exciting.

When reading both papers mentioned above, caution needs to be exercised in interpreting the results. The concepts and data described are quite preliminary in nature and have a long way before they can be realized into clinically-applicable modalities.

click here for more information. Dr. Susan Herring states: "Terrie Cowley, the President of the TMJA, has asked me to add a few comments to the TMJ community to accompany the Science profile of my work. This is very appropriate, because the TMJA and Terrie in particular were in part responsible for my entry into TMJ research about 10 years ago. I was invited to talk about animal models for TMJ research at a 1994 NIH workshop that was attended not only by researchers and clinicians, but also by patients, a real wake-up call for me. At first glance, pigs may not seem the most likely model for human TMJ work, but in fact these omnivorous (and hungry!) mammals have teeth, jaw muscles and jaw joints that are remarkably similar to our own. Even the size is about right, so that surgical procedures and implants aimed at humans can be tried out first on pigs. Our studies have shown that the normal (pig) TMJ is a very dynamic biomechanical area. During chewing, the bones of the TMJ receive a variety of rapidly changing forces. The TMJ disc slides on the bones while its shape is simultaneously deformed. The intricate choreography of these movements is easily disrupted by damage to any part of the TMJ, accounting for its vulnerability. Another important consideration is that the mandibular condyle, the bottom bone of the TMJ, is also the major site of growth for the lower jaw. Overloading of the TMJ in a young individual may inhibit growth and add to deformity. It is our hope that understanding how the parts of the joint work and interact with each other will lead to better therapies, more functional prostheses, and perhaps eventually, biological replacements of damaged joints."

After a lot of wear and tear, the cartilage that has kept the joints running smoothly gives out, and the body has no substitute or repair kit for the valuable tissue. But researchers just might. A bioengineering team has brewed up a liquid polymer gel that can be poured into torn cartilage tissue. Tested on rabbits, the gel adapts to the shape of the tear and becomes the scaffolding for the body's cartilage cells to make new tissue. http://www.nibib.nih.gov/HealthEdu/SciSnippets#Degenerative

Researchers are deciphering the biological changes that can turn pain into a debilitating, chronic state--and they are uncovering new targets for potential painkilling drugs. to view article information, click here.

Click here to view summary (August 2003)

Robert C. Coghill and colleagues at Wake Forest University Baptist Medical Center used magnetic resonance imaging (MRI) to study the brains of individuals who volunteered in pain studies. The researchers report that the parts of the brain involved in experiencing pain were more active in subjects whose rating of pain was greater (on a 1-to-10 scale) than in subjects reporting less pain, lending further weight to studies that there are inherent differences in human pain sensitivity. The 17 volunteers were subjected to heat applied by a heating pad to the lower right leg. The brain areas affected included the primary somatosensory cortex (which receives input on the location and intensity of pain) and the anterior cingulate cortex, which is associated with the emotional aspects of pain-its unpleasantness and suffering components. The report was published in the Proceedings in the National Academy of Sciences in late June, 2003.

After years of being told they have either dental or mental problems that explain their often-excruciating pain, TMJ sufferers are finally being given validation and hope as the result of new genetic research. A group of University of Michigan neuroscientists has identified a single gene linked to the amount of pain a person can tolerate. The research, reported in the journal Science, shows that how much pain you suffer is due, at least in part, to a gene that affects how many endorphins, or natural painkillers, your body produces. An enzyme called COMT, produced by the gene, metabolizes the brain chemical, dopamine, which acts as a signal messenger between brain cells. The researchers found that people with a defective version of COMT were less able to make endorphins, and therefore likely more sensitive to painful stimuli. PET scans have confirmed that this enzyme is much more active in some people's brains than in others. The activity of the enzyme is at least partially dependent on the copies of the gene inherited from one's parents. The COMT gene that contains the amino acid methionine, or met, is less active than if it contained the amino acid valine, or val. Those people with two copies of the met-COMT gene were likely to suffer the most pain. It is extraordinary news for TMJ patients that there is finally a scientifically proven physiological basis to provide some explanation as to the cause of their pain. Because it is genetically linked, predisposition to heightened pain response can even be inherited. Patients who have been told their suffering is psychological now have evidence that their pain is, in truth, physical. Thanks to the work these researchers and others committed to discovering the physiological sources of pain, especially for TMJ and other related chronic pain diseases, there is new hope for research-based therapies. A simple blood test may, in the future, result in predicting which medications would be most effective for an individual sufferer. The study's authors include Jon-Kar Zubieta, Mary Heitzig, Yolanda Smith, Joshua Bueller, Yanjun Xu, Robert Koeppe, and Christian Stohler of the University of Michigan, and Ke Xu and David Goldman of NIAAA. Dr. Stohler has credited the TMJ Association with helping him to remain persistent in pursuit of this research: "If it were not for the encouragement and education of the TMJ Association, we would have long given up…because we were told that what we were pursuing could not be done." This research was conducted when Dr. Stohler was at the University of Michigan. Currently, Dr. Stohler is the Dean of the University of Maryland Dental School, Baltimore, Maryland. Dr. Stohler is also a Scientific Advisor to The TMJ Association.

viewTMJ Science.