of the tissues of the joint, limitation of function (e.g. restricted mandibular movements), and joint pain. psychosocial factors emotional stress (anxiety, depression, anger) may increase pain by causing autonomic, visceral and skeletal activity and by reduced inhibition via the descending pathways of the limbic system. the interactions of these biological systems have been described as a vicious "anxiety-pain-tension" cycle which is thought to be frequently involved in tmd. put simply, stress and anxiety cause grinding of teeth and sustained muscular contraction in the face. this produces pain which causes further anxiety which in turn causes prolonged muscular spasm at trigger points, vasoconstriction, ischemia and release of pain mediators. the pain discourages use of the masticatory system (a similar phenomenon in other chronic pain conditions is termed "fear avoidance" behavior), which leads to reduced muscle flexibility, tone, strength and endurance. this manifests as limited mouth opening and a sensation that the teeth are not fitting properly. persons with tmd have a higher prevalence of psychological disorders than people without tmd. people with tmd have been shown to have higher levels of anxiety, depression, somatization and sleep deprivation, and these could be considered important risk factors for the development of tmd. in the 6 months before the onset, 50–70% of people with tmd report experiencing stressful life events (e.g. involving work, money, health or relationship loss). it has been postulated that such events induce anxiety and cause increased jaw muscle activity. muscular hyperactivity has also been shown in people with tmd whilst taking examinations or watching horror films. others argue that a link between muscular hyperactivity and tmd has not been convincingly demonstrated, and that emotional distress may be more of a consequence of pain rather than a cause. bruxism main article: bruxism bruxism is an oral parafunctional activity where there is excessive clenching and grinding of the teeth. it can occur during sleep or whilst awake. the cause of bruxism itself is not completely understood, but psychosocial factors appear to be implicated in awake bruxism and dopaminergic dysfunction and other central nervous system mechanisms may be involved in sleep bruxism. if tmd pain and limitation of mandibular movement are greatest upon waking, and then slowly resolve throughout the day, this may indicate sleep bruxism. conversely, awake bruxism tends to cause symptoms that slowly get worse throughout the day, and there may be no pain at all upon waking. the relationship of bruxism with tmd is debated. many suggest that sleep bruxism can be a causative or contributory factor to pain symptoms in tmd. indeed, the symptoms of tmd overlap with those of bruxism. others suggest that there is no strong association between tmd and bruxism. a systematic review investigating the possible relationship concluded that when self-reported bruxism is used to diagnose bruxism, there is a positive association with tmd pain, and when more strict diagnostic criteria for bruxism are used, the association with tmd symptoms is much lower. self-reported bruxism is probably a poor method of identifying bruxism. there are also very many people who grind their teeth and who do not develop tmd. bruxism and other parafunctional activities may play a role in perpetuating symptoms in some cases. other parafunctional habits such as pen chewing, lip and cheek biting (which may manifest as morsicatio buccarum or linea alba), are also suggested to contribute to the development of tmd. other parafunctional activities might include jaw thrusting, excessive gum chewing, nail biting and eating very hard foods. trauma trauma, both micro and macrotrauma, is sometimes identified as a possible cause of tmd; however, the evidence for this is not strong. prolonged mouth opening (hyper-extension) is also suggested as a possible cause. it is thought that this leads to microtrauma and subsequent muscular hyperactivity. this may occur during dental treatment, with oral intubation whilst under a general anesthetic, during singing or wind instrument practice (really these can be thought of as parafunctional activities). damage may be incurred during violent yawning, laughing, road traffic accidents, sports injuries, interpersonal violence, or during dental treatment, (such as tooth extraction). it has been proposed that a link exists between whiplash injuries (sudden neck hyper-extension usually occurring in road traffic accidents), and the development of tmd. this has been termed "post-traumatic tmd", to separate it from "idiopathic tmd". despite multiple studies having been performed over the years, the cumulative evidence has been described as conflicting, with moderate evidence that tmd can occasionally follow whiplash injury. the research that suggests a link appears to demonstrate a low to moderate incidence of tmd following whiplash injury, and that ptmd has a poorer response to treatment than tmd which has not developed in relation to trauma. occlusal factors occlusal factors as an etiologic factor in tmd is a controversial topic. abnormalities of occlusion (problems with the bite) are often blamed for tmd but there is no evidence that these factors are involved. occlusal abnormalities are incredibly common, and most people with occlusal abnormalities do not have tmd. although occlusal features may affect observed electrical activity in masticatory muscles, there are no statistically significant differences in the number of occlusal abnormalities in people with tmd and in people without tmd. there is also no evidence for a causal link between orthodontic treatment and tmd. the modern, mainstream view is that the vast majority of people with tmd, occlusal factors are not related. theories of occlusal factors in tmd are largely of historical interest. a causal relationship between occlusal factors and tmd was championed by ramfjord in the 1960s. a small minority of dentists continue to prescribe occlusal adjustments in the belief that this will prevent or treat tmd despite the existence of systematic reviews of the subject which state that there is no evidence for such practices, and the vast majority of opinion being that no irreversible treatment should be carried out in tmd (see occlusal adjustment). genetic factors tmd does not obviously run in families like a genetic disease. it has been suggested that a genetic predisposition for developing tmd (and chronic pain syndromes generally) could exist. this has been postulated to be explained by variations of the gene which codes for the enzyme catechol-o-methyl transferase (comt) which may produce 3 different phenotypes with regards pain sensitivity. comt (together with monoamine oxidase) is involved in breaking down catecholamines (e.g. dopamine, epinephrine, and norepinephrine). the variation of the comt gene which produces less of this enzyme is associated with a high sensitivity to pain. females with this variation, are at 2–3 times greater risk of developing tmd than females without this variant. however this theory is controversial since there is conflicting evidence. hormonal factors since females are more often affected by tmd than males, the female sex hormone estrogen has been suggested to be involved. the results of one study suggested that the periods of highest pain in tmd can be correlated with rapid periods of change in the circulating estrogen level. low estrogen was also correlated to higher pain. in the menstrual cycle, estrogen levels fluctuate rapidly during ovulation, and also rapidly increases just before menstruation and rapidly decreases during menstruation. post-menopausal females who are treated with hormone replacement therapy are more likely to develop tmd, or may experience an exacerbation if they already had tmd. several possible mechanisms by which estrogen might be involved in tmd symptoms have been proposed. estrogen may play a role in modulating joint inflammation, nociceptive neurons in the trigeminal nerve, muscle reflexes to pain and μ-opioid receptors. possible associations tmd has been suggested to be associated with other conditions or factors, with varying degrees of evidence and some more commonly than others. 75% of people with tmd qualify for a fibromyalgia diagnosis and, conversely, 18% of people with fibromyalgia met diagnostic criteria for tmd. a possible link between many of these chronic pain conditions has been hypothesized to be due to shared pathophysiological mechanisms, and they have been collectively termed "central sensitivity syndromes", although other apparent associations cannot be explained in this manner. recently a plethora of research has substantiated a causal relationship between tmd and obstructive sleep apnea (osa). severe tmd restricts oral airway opening, and can result in a retrognathic posture that results in glossal blockage of the oropharynx as the tongue relaxes in sleep. this mechanism is exacerbated by alcohol consumption, as well as other chemicals that result in reduced myotonic status of the oropharynx. obstructive sleep apnea. headache. chronic neck pain. chronic back pain. systemic joint laxity. rheumatoid arthritis. irritable bowel syndrome. interstitial cystitis. regular scuba diving. pathophysiology left temporomandibular joint, lateral view.left tmj, medial view, showing sphenomandibular and stylomandibular ligaments.sagittal tmj cross-section showing articular eminence, articular disc, and upper and lower joint spaces. temporomandibular joints main article: temporomandibular joint the temporomandibular joints are the dual articulation of the mandible with the skull. each tmj is classed as a "ginglymoarthrodial" joint since it is both a ginglymus (hinging joint) and an arthrodial (sliding) joint, and involves the condylar process of the mandible below, and the articular fossa (or glenoid fossa) of the temporal bone above. between these articular surfaces is the articular disc (or meniscus), which is a biconcave, transversely oval disc composed of dense fibrous connective tissue. each tmj is covered by a fibrous capsule. there are tight fibers connecting the mandible to the disc, and loose fibers which connect the disc to the temporal bone, meaning there are in effect 2 joint capsules, creating an upper joint space and a lower joint space, with the articular disc in between. the synovial membrane of the tmj lines the inside of the fibrous capsule apart from the articular surfaces and the disc. this membrane secretes synovial fluid, which is both a lubricant to fill the joint spaces, and a means to convey nutrients to the tissues inside the joint. behind the disc is loose vascular tissue termed the "bilaminar region" which serves as a posterior attachment for the disc and also fills with blood to fill the space created when the head of the condyle translates down the articular eminence. due to its concave shape, sometimes the articular disc is described as having an anterior band, intermediate zone and a posterior band. when the mouth is opened, the initial movement of the mandibular condyle is rotational, and this involves mainly the lower joint space, and when the mouth is opened further, the movement of the condyle is translational, involving mainly the upper joint space. this translation movement is achieved by the condylar head sliding down the articular eminence, which constitutes the front border of the articular fossa. the function of the articular eminence is to limit the forwards movement of the condyle. the ligament directly associated with the tmj is the temporomandibular ligament, also termed the lateral ligament, which really is a thickening of the lateral aspect of the fibrous capsule. the stylomandibular ligament and the sphenomandibular ligament are not directly associated with the joint capsule. together, these ligaments act to restrict the extreme movements of the joint. muscles of mastication main article: muscles of mastication the muscles of mastication are paired on each side and work together to produce the movements of the mandible. the main muscles involved are the masseter, temporalis and medial and lateral pterygoid muscles. left medial and lateral pterygoid muscles left temporalis muscle left masseter muscle (red highlight) they can be thought of in terms of the directions they move the mandible, with most being involved in more than one type of movement due to the variation in the orientation of muscle fibers within some of these muscles. protrusion – lateral and medial pterygoid. retraction – posterior fibers of temporalis (and the digastric and geniohyoid muscles to a lesser extent). elevation – anterior and middle fibers of temporalis, the superficial and deep fibers of masseter and the medial pterygoid. lateral movements – medial and lateral pterygoid (the ipsilateral temporalis and the pterygoid muscles of the contralateral side pull the mandible to the ipsilateral side). each lateral pterygoid muscle is composed of 2 heads, the upper or superior head and the lower or inferior head. the lower head originates from the lateral surface of the lateral pterygoid plate and inserts at a depression on the neck of mandibular condyle, just below the articular surface, termed the pterygoid fovea. the upper head originates from the infratemporal