Alterations in Temporal Aspects of Pain Processing and Modulation

描述（由申请人提供）：尽管慢性疼痛的严重程度和频率，但目前的医学缺乏用于治疗选择的诊断工具，以持续有效地缓解个体疼痛。痛觉过敏和异常性疼痛的症状有助于临床诊断，然而，敏感性的更微妙的时间变化也可能代表重要的诊断终点。疼痛后感觉，在触觉/热刺激结束后很长时间内疼痛的异常持续性，在慢性疼痛中经常观察到，并且可能与由于疼痛调制中断而导致的伤害性信息的时间处理改变有关。为了更好地了解如何伤害性处理是暂时改变临床状态，结合心理物理和功能磁共振成像研究将检查健康受试者和CRPS（复杂区域疼痛综合征）患者，以解决以下具体目标：目的1：确定时间改变疼痛感知的中枢致敏的结果。目的2：确定支持伤害性刺激时间加工的神经药理学底物。目的3：确定神经生理学相关的暂时改变疼痛感知慢性疼痛。偏置镇痛是一种可能代表内源性抗伤害性机制在伤害性刺激的时间维度加工过程中的动态参与的现象。评估抵消镇痛和受试者/患者对急性疼痛热刺激的反应，持续时间和缓慢下降率将使我们能够阐明疼痛处理的时间方面如何在中枢致敏（辣椒素热致敏和慢性疼痛）和药理学操作（阿片激动剂和拮抗剂）状态下发生改变。然后，我们将这些心理物理反应的变化与观察到的生理异常，使用功能成像的皮质和皮质下区域与BOLD（血氧水平依赖）和ASL（动脉自旋标记）功能磁共振成像设计。这项奖学金申请中的拟议研究旨在解决对疼痛机制以及慢性疼痛患者的伤害性处理如何发生显着改变的理解不足。研究支持有害信息时间处理的机制可能有助于改善病理性疼痛状态的临床评估和治疗。

DESCRIPTION (provided by applicant): Despite the severity and frequency of chronic pain, current medicine lacks diagnostic tools for treatment selection to consistently and effectively alleviate pain on an individual basis. The symptoms of hyperalgesia and allodynia are helpful for clinical diagnoses, however, more subtle temporal changes in sensitivity may also represent important diagnostic endpoints. Painful aftersensations, the abnormal persistence in pain long after the end of a tactile / thermal stimulus, are frequently observed in chronic pain and may be related to altered temporal processing of nociceptive information due to disrupted pain modulation. In order to better understand how nociceptive processing is temporally altered in clinical states, a combination of psychophysical and fMRI studies will examine healthy subjects and CRPS (complex regional pain syndrome) patients to address the following specific aims: Aim 1: To identify temporal alterations in pain perception as a consequence of central sensitization. Aim 2: To identify neuropharmacological substrates supporting temporal processing of noxious stimuli. Aim 3: To identify neurophysiological correlates of temporally altered pain perception in chronic pain. Offset analgesia is a phenomenon that may represent the dynamic engagement of endogenous anti- nociceptive mechanisms during the processing of temporal dimensions of noxious stimuli. Assessment of offset analgesia and subjects/patients responses to acute painful heat stimuli with variable durations and slow fall rates will allow us to elucidate how temporal aspects of pain processing are altered in states of central sensitization (capsaicin-heat sensitization and chronic pain) and pharmacological manipulation (opioid agonist and antagonist). We will then correlate these changes in psychophysical responses to observed physiological abnormalities using functional imaging of cortical and subcortical regions with BOLD (blood oxygenation level dependent) and ASL (arterial spin labeling) fMRI designs. The proposed research in this fellowship application aims to resolve the lack in understanding of pain mechanisms and how nociceptive processing is dramatically altered in chronic pain patients. The investigation of mechanisms that support temporal processing of noxious information may contribute to and improve clinical assessment and treatment of pathological pain states.