The etiology and pathogenesis of ongoing pain in the muscles of mastication and the temporomandibular joint (TMJ), known as temporomandibular disorders (TMDs), still are not understood completely. There are a considerable number of animal and human studies suggesting that an increased concentration of the excitatory amino acid glutamate in the masticatory muscles and TMJ may be one of the factors responsible for the development and maintenance of chronic myofascial TMD pain. Glutamate injection into the masseter muscle has proven to be a safe reliable transient myofascial TMD pain model. N-methyl-d-aspartate (NMDA) receptor antagonists such as ketamine can attenuate glutamate-evoked pain that suggests that glutamate acts, at least in part, on peripheral NMDA receptors to evoke muscle and joint pain. Moreover, it has been suggested that there may be some sex-related differences in these mechanisms that may be influenced by sex hormones.
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