The purpose of this program announcement is to stimulate research on discovering etiological and pathophysiological mechanisms underlying a set of chronic, comorbid conditions associated with temporomandibular joint and muscle disorders (TMJMDs). TMJMDs are a complex collection of diseases involving one or more tissues of the TMJ and facial musculature. Primary symptoms include chronic pain in facial muscles and limited and painful movement of the jaw. In addition, these and other symptoms of TMJMD can occur together with other chronic illnesses such as fibromyalgia, atypical face pain, trigeminal neuralgia, chronic fatigue syndrome, multiple chemical sensitivity, irritable bowel syndrome, complex regional pain syndrome, migraine headache, speech hearing, swallowing, balance, smell, and taste disorders, and certain cardiovascular diseases. This program announcement seeks research applications that use state-of-the-art, multidisciplinary and interdisciplinary approaches to discover molecular, physiological, and behavioral mechanisms responsible for the overlapping symptoms manifested in the set of disorders that may co-exist with TMJMD. These applications may have as their research focus the chronic, comorbid conditions themselves or TMJMDs, provided that the aims and goals of the project are to discover biological mechanisms linking the comorbidities. While the overarching goal of this announcement is to arrive at a better understanding of potential mechanisms underlying TMJMDs as related to the variety of comorbidities associated with them, it is expected that no single research project will be able to accomplish this. Applicants are, therefore, encouraged to focus their attention on a particular pathway and a specific disease that is comorbid with TMJMD.