Norman F. Capra - US grants

Physiological studies suggest that sensory receptors located in the temporomandibular joint (TMJ), the muscles of mastication, and the periodontal ligament (PDL) are involved in the perception of jaw position and jaw movements (mandibular kinesthesia). The proposed studies will address several important anatomical and functional issues related to the organization of sensory receptors and the primary afferent neurons that innervate these structures. Using the techniques of anterograde and transganglionic transport of wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP), injections will be made into the spinal tract of the trigeminal nerve and into the trigeminal mesencephalic nucleus and tract of adult cats. Selected masticatory muscles and the TMJ capsule will be processed using HRP histochemistry to unequivocally identify, categorize, and map the types of receptors located in these structures. The location of the somata and the central terminations of primary afferent neurons that innervate receptors in the muscles of mastication and the PDL will be determined in the studies mentioned above and by a series of "double label" experiments involving injections of retrogradely transported fluorescent dye and WGA-HRP in selected masticatory muscles and the PDL. Combined anatomical and physiological studies will be performed to identify neurons in the brainstem that receive primary afferent information from receptors in orofacial structures and that respond to experimentally imposed movements of the jaw. The receptive fields of movement sensitive neurons will be determined by electrical or natural stimulation in the periphery. Angular and rate sensitivity of identified neurons will be measured using an angular position transducer. Physiological methods will be used to determine whether the identified cells receive direct input from primary afferent neurons (e.g., latency measurements and following characteristics to high frequency electrical stimulation). Antidromic stimulation techniques will be used to determine whether the identified neurons project to the ventrobasal thalamus. After physiological characterization, WGA-HRP will be iontophoretically injected from the recording electrode. HRP histochemistry will allow the identification of brainstem nuclei that contain movement sensitive neurons and also central neurons that project to these regions. These central neurons may be important in the modulation of kinesthetic input. These data will further our overall goal of characterizing the anatomical and functional properties of neurons involved in mandibular kinesthesis.

biomedical equipment purchase;

DESCRIPTION (Adapted from the investigator's Abstract): The goal of the proposal is to understand how muscle pain associated with temporomandibular disorders (TMD) affects neuromotor performance in primates. Current evidence suggests that at least some myogenous jaw pain in humans causes a protective adaptation response, in which there is decreased activity in agonist muscles, and increased activity in antagonist muscles, resulting in restricted ranges of jaw motion. Currently, a hypothetical brainstem model has been proposed to explain this, but it is equally possible that higher levels of motor control are involved, such as the motor cortex, in addition to, or instead of, the brainstem. Though conscious responses to pain, and control of jaw muscle contraction both involve the sensorimotor cortex, the region's potential contribution to the protective adaptation response has not been studied. Since the applicants have developed a suitable animal model for producing transient jaw muscle pain in the awake monkey (Macaca mulatta) and for observing its effects on voluntary jaw motion and jaw position, the first aim therefore is to carry out a parametric analysis of normal jaw motion and muscle activity during stereotyped motor tasks and automatic chewing, and to repeat the experiment in the presence of induced muscle pain. The second aim is to define relationships between the types and locations of corticomotoneuronal activity, and the same peripheral variables associated with these acts in normal animals. The third aim is to repeat this study of the motor cortex in the presence of induced muscle pain. The applicant hypothesizes that cortical neurons provide signals correlated with the initiation and execution of jaw movements and the maintenance of jaw positions, and that the signals change during the conscious pain experience in such a way as alter muscle contraction patterns, and subsequent jaw motion. They consider that their preliminary data support this proposition. The alternative hypothesis proposed is that this change in cortical signalling does not occur, in which case the applicant will conclude that the pain-adaptation response is due primarily to brainstem mechanisms. The applicant believes the study is significant because it can provide a better understanding of cortical influences in the control of jaw movement generally, and in particular, define the cortex's role in human motor responses to jaw muscle pain.

DESCRIPTION: (provided by applicant) The goal of this program is to provide rich research opportunities to a diverse population of college, graduate, dental, medical, postgraduate and combined DDS/PhD and MD/PhD) student; and to junior and mid-career faculty seeking new research initiatives. The training program that we are proposing capitalizes on the unique geographic proximity between major medical centers in the City of Baltimore and Washington, D.C. We have four major thematic areas of strength in clinical and basic research and have identified over fifty expert faculty who will provide mentoring for students and faculty in order to produce individuals who are likely to respond to the health-related challenges that face the field of dentistry in the future. Our thematic areas of expertise are Hard Tissue and Neoplastic Disease, Infectious and Antoimmune Diseases, Oral and Craniofacial Chronic Sensory Disorders, and Oral and Craniofacial Motor Disorders. Primary emphasis will be placed on cross-disciplinary approaches with emphasis on the integration of basic, translational and clinical research in each student program. Our major objective is to provide a horizontal organizational structure in which basic and clinical research opportunities are integrated across disciplines and a vertical organizational structure of career development and mentoring that spans from college students to mid-career faculty. We are committed to implementation of an organizational structure that enhances training opportunities for underrepresented minorities and women. A diverse student population at Howard University, the University of Maryland Baltimore County, and Morgan State University will have the opportunity to receive training in biomedical research. Almost all the faculty mentors have external research support and are appointed at the University of Maryland Dental School, University of Maryland Medical School, the Johns Hopkins University and the intramural program of the National Institutes of Health.