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The temporomandibular joint (TMJ) may be affected by inflammatory,traumatic, infectious, congenital, developmental, and neoplastic diseases,as seen in other joints. However, the most common affliction of the TMJ andmasticatory apparatus is a group of functional disorders with associated pain thatoccurs predominantly in women and was previously known as the TMJ pain dysfunctionsyndrome. Since 1978, there have been substantial changes in the study ofetiologic factors, pathophysiology, diagnosis, and management of what are nowcalled temporomandibular disorders.1,2 The general perception that all symptoms

in the head, face, and jaw region without an identifiable cause constitute a TMJproblem is clearly unfounded.Temporomandibular disorders are defined as a subgroup of craniofacial painproblems that involve the TMJ, masticatory muscles, and associated head and neckmusculoskeletal structures. Patients with temporomandibular disorders most frequentlypresent with pain, limited or asymmetric mandibular motion, and TMJsounds.3,4 The pain or discomfort is often localized to the jaw, TMJ, and musclesof mastication. Common associated symptoms include ear pain and stuffiness, tinnitus,dizziness, neck pain, and headache. In some cases, the onset is acute andsymptoms are mild and self-limiting. In other patients, a chronic temporomandibular

disorder develops, with persistent pain and physical, behavioral, psychological,and psychosocial symptoms similar to those of patients with chronic painsyndromes in other areas of the body5-7 (e.g., arthritis, low back pain, chronic headache,fibromyalgia, and chronic regional pain syndrome), all requiring a coordinatedinterdisciplinary diagnostic and treatment approach.Temporomandibular disorders are classified as one subtype of secondary headachedisorders by the International Headache Society in the International Classificationof Headache Disorders II (2004).8 The American Academy of Orofacial Painhas expanded on this classification, as shown in Table 1.9The prevalence among adults in the United States of at least one sign of temporomandibulardisorders is reported as 40 to 75% and among those with at least

one symptom, 33%.7,9,10 TMJ sounds and deviation on opening the jaw occur in approximately50% of otherwise asymptomatic persons; these are considered withinthe range of normal and do not require treatment.11 Other signs, such as decreasedmouth opening and occlusal changes, occur in fewer than 5% of the general population.12 Temporomandibular disorders are most commonly reported in young tomiddle-aged adults (20 to 50 years of age). The female-to-male ratio of patientsseeking care has been reported as ranging from 3:1 to as high as 9:1.10,13 Despitethe high prevalence of temporomandibular disorders, signs, and symptoms, only5 to 10% of those with symptoms require treatment, given the wide spectrum ofsymptoms and the fact that the natural history of this disorder suggests that inup to 40% of patients the symptoms resolve spontaneously.7,14

In this review we focus on the most common forms of temporomandibular dis-Copyright 2008 Massachusetts Medical Society. All rights reserved.Downloaded from www.nejm.org by MICHELE JEHENSON MD on December 22, 2008 .Th e new england journal o f medicine2694 n engl j med 359;25 www.nejm.org december 18, 2008orders seen by the primary care physician: myofascialpain disorder, intra-articular disk derangementdisorders, osteoarthritis, and rheumatoidarthritis.ETIOLOGYIn 1934, James Costen, an otolaryngologist, evaluated

13 patients who presented with pain in ornear the ear, tinnitus, dizziness, a sensation of earfullness, and difficulty swallowing.15 He observedthat these patients had many missing teeth and,as a result, their mandibles were overclosed. The

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symptoms seemed to diminish when their missingteeth were replaced and the proper verticaldimension of the occlusion was restored. Costenbelieved that the malocclusion and improper jawposition were the cause of both of the disturbedfunction of the temporomandibular joint andthe associated facial pain. Thereafter, the emphasisof treatment for this condition focused on altering

the affected patients dental occlusion.More recently, advances in the understandingof joint biomechanics, neuromuscular physiology,autoimmune and musculoskeletal disorders, andpain mechanisms have led to changes in our understandingof the cause of temporomandibulardisorders. The cause is now considered multifactorial,with biologic, behavioral, environmental,social, emotional, and cognitive factors, alone orin combination, contributing to the developmentof signs and symptoms of temporomandibular

disorders.9 Some of the current views of the pathogenesisof muscle and intra-articular disordersare shown in Figure 1.Various forms of trauma to the TMJ structures(ligaments, articular cartilage, articular disk, andbone) can lead to intra-articular biochemical alterationsthat have been shown to produce oxidativestress and to generate free radicals. Subsequentinflammatory changes in synovial fluidwith the production of a variety of inflammatorycytokines can then lead to alteration in the functioningof normal tissues and degenerative diseasein the TMJ.16-20Genetic marker studies of genes involved withcatecholamine metabolism and adrenergic receptorssuggest that certain polymorphisms (e.g., inthe catechol O-methyltransferase [COMT] gene)might be associated with changes in pain responsivenessand pain processing in patients withchronic temporomandibular disorders.21-23 Differencesin pain modulation have been reported between

women and men with these disorders, withwomen showing decreased thresholds to noxiousstimuli and more hyperalgesia. In addition, somestudies suggest that the affective component ofpain in women with temporomandibular disordersmay be enhanced during the low-estrogen phaseof the menstrual cycle.24-27Functional brain imaging studies showing