CNS Processes Underlying Pain Regulation and Persistence

描述(由申请人提供)： 该计划项目的中心主题是，当中枢神经系统调节系统功能失调时，疼痛体验的维度(例如，疼痛强度、局部性和持续性)可能远远超过基于外周组织损伤或病理的预期。到目前为止，缺乏直接评估和表征这些系统状态的方法阻碍了对中枢神经系统疼痛调节机制的理解。为了解决这一差距，将使用最先进的人类心理物理和神经成像方法(结合定量EEG和功能磁共振成像)在大脑皮层水平评估被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)的患者以及正常健康受试者的中枢神经系统疼痛状况和触摸调节机制。心理物理学的发现表明，拟议的心理物理和神经成像实验将针对三个这样的过程：扩散伤害性抑制控制(DNIC，疼痛抑制疼痛)、触摸门(疼痛抑制机械接收)和痛门(机械接收抑制疼痛)。此外，还将使用纵向流行病学方法来确定中枢神经系统调节系统的异常是否预示着其他健康的年轻成年女性TMD的后续发展。指导这项工作的基本假设是，中枢神经系统调节系统中的功能障碍(S)增加了疼痛敏感性，并代表了一个重要的风险因素，导致中枢敏感化的发展，从而导致持续的肌肉骨骼疼痛状况，如肌源性TMD。 该计划项目的长期目标是：1)获得实验证据，能够对调节中枢敏感化障碍患者表现出的剧烈、异常广泛和持续性疼痛的生理/生物过程进行机械性解释和量化。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敏感化和疼痛调节障碍相关的外周和中枢神经系统病理生理学。3)建立一种环境，使基础科学家和对中枢性疼痛及其调节感兴趣的临床医生之间能够进行有效和富有成效的互动。4)创造一种研究环境，促进将基础科学成果转化为治疗措施，以治疗持续性肌肉骨骼疼痛。

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.