CNS Processes Underlying Pain Regulation and Persistence

描述（由申请人提供）： 该项目的中心主题是疼痛体验的维度（例如，疼痛强度、定位和持续性）可以远远超过基于外周组织损伤或病理学的预期，只要CNS调节系统功能障碍。到目前为止，缺乏直接评估和表征这些系统的状态的方法，阻碍了了解中枢神经系统疼痛调节机制的进展。为了解决这一差距，国家的最先进的人类心理物理学和神经影像学方法（结合定量脑电图和功能磁共振成像）将被用来评估，在大脑皮层的水平，CNS疼痛和触摸调节机制的状态诊断为纤维肌痛综合征（FM）和肌源性颞下颌关节功能障碍（TMD）的患者，并在正常的健康受试者。心理物理学的研究结果表明，在三个这样的过程中，将有针对性的拟议的心理物理学和神经影像学实验异常：弥漫性有害抑制控制（DNIC，疼痛抑制疼痛），触摸门（抑制机械感受疼痛），和疼痛门（抑制疼痛机械感受）。此外，纵向流行病学的方法将被用来确定是否异常中枢神经系统的调节系统预测随后的发展，TMD在其他健康的年轻成年女性。指导这项工作的主要假设是CNS调节系统内的功能障碍增加了疼痛敏感性，并代表了导致持续性肌肉骨骼疼痛状况（如肌源性TMD）的中枢致敏发展的重要风险因素。 本计划项目的长期目标是：1）获得实验证据，从而能够对介导中枢致敏性疾病患者所表现出的强烈、异常广泛和持续性疼痛的生理/生物过程进行机械解释和量化。2)开发和验证新的心理生理学和神经生理学方法，允许定量评估与中枢致敏和疼痛调节障碍相关的外周和CNS病理生理学。3)建立一个环境，使基础科学家和临床医生之间的有效和富有成效的互动感兴趣的中枢疼痛及其调节。4)创造一个研究环境，促进将基础科学发现转化为治疗持续性肌肉骨骼疼痛的治疗干预措施。

DESCRIPTION (provided by applicant): The central theme of this Program Project is that the dimensions of the pain experience (e.g., pain intensity, localization, and persistence) can far exceed those expected on the basis of peripheral tissue injury or pathology whenever CNS regulatory systems are dysfunctional. Up to now, a lack of methods for the direct evaluation and characterization of the status of these systems has deterred progress in understanding CNS pain regulatory mechanisms. To address this gap, state-of-the-art human psychophysical and neuroimaging methods (combined quantitative EEG and fMRI) will be used to evaluate, at the level of the cerebral cortex, the status of CNS pain and touch regulatory mechanisms in patients diagnosed with fibromyalgia syndrome (FM) and with myogenous temporomandibular dysfunction (TMD), and in normal healthy subjects. Psychophysical findings have suggested abnormalities in three such processes that will be targeted by the proposed psychophysical and neuroimaging experiments: diffuse noxious inhibitory control (DNIC, inhibition of pain by pain), the touch gate (inhibition of mechanoreception by pain), and the pain gate (inhibition of pain by mechanoreception). In addition, longitudinal epidemiological approaches will be used to determine whether abnormalities in CNS regulatory systems predict the subsequent development of TMD in otherwise healthy young adult females. The primary hypothesis that guides this work is that dysfunction(s) within CNS regulatory systems increases pain sensitivity and represents an important risk factor that contributes to the development of central sensitization which leads to persistent musculoskeletal pain conditions like myogenous TMD. The long-term goals of this Program Project are to: 1) To obtain experimental evidence enabling mechanistic interpretation and quantification of the physiological/biological processes that mediate the intense, abnormally widespread, and persistent pain exhibited by patients with disorders of central sensitization. 2) To develop and validate novel psychophysiological and neurophysiological approaches that permit quantitative assessment of the peripheral and CNS pathophysiology associated with disorders of central sensitization and pain regulation. 3) To establish an environment that enables effective and productive interactions between basic scientists and clinicians interested in central pain and its regulation. 4) To generate a research environment that facilitates translation of basic science findings into therapeutic interventions for the treatment of persistent musculoskeletal pain.