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.
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.