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性和频率，目前的医学缺乏诊断工具来选择治疗方法，以持续有效地减轻个体的疼痛。痛觉过敏和异常痛觉的症状有助于临床诊断，然而，更细微的敏感性时间变化也可能代表重要的诊断终点。疼痛后感，即在触觉/热刺激结束后很长一段时间内疼痛的异常持续，在慢性疼痛中经常观察到，可能与疼痛调节中断导致的伤害性信息的时间加工改变有关。为了更好地理解临床状态下痛觉加工的时间改变，心理物理和功能磁共振成像的结合研究将对健康受试者和复杂区域疼痛综合征（CRPS）患者进行检查，以解决以下具体目标：目的1：确定中枢致敏导致的疼痛感知的时间改变。目的2：确定支持有害刺激颞加工的神经药理学基础。目的3：确定慢性疼痛中暂时改变的疼痛感知的神经生理学相关性。补偿性镇痛是一种可能代表内源性抗伤害性机制在有害刺激的时间维度加工过程中动态参与的现象。评估补偿镇痛和受试者/患者对不同持续时间和缓慢下降率的急性疼痛热刺激的反应，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，我们将使用BOLD（血氧水平依赖）和ASL（动脉自旋标记）功能磁共振成像设计，将这些心理物理反应的变化与观察到的生理异常联系起来。本研究旨在解决慢性疼痛患者对疼痛机制的理解不足以及伤害性加工如何显著改变的问题。研究支持有害信息颞加工的机制可能有助于并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.