Brainstem Mechanisms of Craniofacial Muscle Pain

描述（由申请人提供）：在K22教师过渡奖期间，我的目标是在专家导师的指导下获得口腔和颅面疼痛领域的专业知识，并成功过渡到独立调查员。我们制定了一个全面的计划，以确保我在职业发展的许多方面都能及时取得进展。这项研究的科学目标是全面了解三叉神经脑干在颅面肌肉疼痛处理中的机制。缺乏关于咀嚼肌疾病相关疼痛如何发展和持续的科学信息，阻碍了我们理解潜在病理生理学以及诊断和治疗TMD和其他咀嚼障碍的能力。三叉神经脊核（VSP）中感觉处理的独特组织使介导颅面肌肉疼痛的神经机制进一步复杂化。我们对急性和慢性肌肉疼痛的各个方面如何在VSP的不同细分中以及作为一个综合系统进行处理的了解很少。我建议，有害的输入咀嚼肌分布在整个VSP。每个亚核有助于急性和炎性口面部肌肉疼痛的功能不同的方面，但通过核内连接存在显着的亚核之间的相互作用。首先，将检查接受有害肌肉输入的三叉神经元的分布和传入会聚。还将研究炎性肌肉疼痛对神经元激活的模式和程度以及深部和皮肤敏感性的神经可塑性变化的影响。最后，将通过核内和传出投射模式研究各亚核之间的相互作用和功能作用。导师和咨询委员会成员都很有资格为拟议的实验提供必要的培训，并对我的进展进行客观评估。大学和系全力支持我的发展，并将提供实现我的目标所需的环境。在这个过渡奖期间的培训将使我能够继续未来的研究，导致NIH R01拨款提案的发展，这将进一步加深我们对颅面肌肉疼痛的神经生理学和神经化学机制的基本理解。

DESCRIPTION (provided by applicant): My objective during the K22 Faculty Transition Award is to gain expertise in the field of oral and craniofacial pain under the guidance of expert mentors and make a successful transition into an independent investigator. A comprehensive plan was designed to ensure timely progress of many facets in my career development. The scientific goal of the proposed research is to provide an overall understanding of the trigeminal brainstem mechanisms in craniofacial muscle pain processing. The lack of scientific information on how pain associated with masticatory muscle disorders develop and persist has hampered our ability to understand the underlying pathophysiology, and to diagnose and treat TMD and other masticatory disorders. Neural mechanisms mediating craniofacial muscle pain are further complicated by the unique organization of sensory processing in the trigeminal spinal nucleus (Vsp). We have very little understanding of how various aspects of acute and chronic muscle pain are processed across different subdivisions in the Vsp and as an integrated system. I propose that noxious inputs from masticatory muscles are distributed throughout the entire Vsp. Each subnucleus contributes to functionally different aspects of acute and inflammatory orofacial muscle pain, but significant interactions between the subnuclei exist via the intranuclear connections. Initially, the distribution and afferent convergence of trigeminal neurons that receive noxious muscle input will be examined. The effects of inflammatory muscle pain on the pattern and extent of neuronal activation and neuroplastic changes in both deep and cutaneous sensibilities will also be studied. Finally, interactions between the subnuclei and functional role of each subnucleus will be studied by intranuclear and efferent projection patterns. The mentors and advisory committee members are well qualified to provide necessary training for proposed experiments and objective evaluation of my progress. The University and the Department are fully supportive of my development and will provide the environment necessary to realize my goals. The training during this transition award will enable me to pursue future studies leading to the development of a NIH R01 grant proposal that will further our basic understanding of neurophysiological and neurochemical mechanisms of craniofacial muscle pain.