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很高，但目前的医学缺乏用于治疗选择的诊断工具，无法持续有效地减轻个体疼痛。痛觉过敏和痛觉异常的症状有助于临床诊断，然而，敏感度的更微小的时间变化也可能代表重要的诊断终点。疼痛后感是指在触觉/热刺激结束后很长一段时间内疼痛的异常持续，常见于慢性疼痛，可能与痛觉调制中断引起的伤害性信息的时间加工改变有关。为了更好地了解痛觉加工在临床状态下是如何在时间上发生改变的，一项心理物理和功能磁共振相结合的研究将检查健康受试者和复杂区域疼痛综合征(CRPS)患者，以解决以下特定目标：目的1：确定中枢敏化导致痛觉的时间改变。目的2：寻找支持伤害性刺激时间加工的神经药理基础。目的3：确定慢性疼痛时痛觉暂时性改变的神经生理学相关性。偏置镇痛是在伤害性刺激的时间维度加工过程中，内源性抗伤害机制的动态参与的一种现象。评估疼痛补偿和受试者/患者对具有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在中枢敏化(辣椒素-热敏化和慢性疼痛)和药物操纵(阿片类激动剂和拮抗剂)状态下，疼痛处理的时间方面是如何改变的。然后，我们将通过使用BOLD(血氧水平依赖)和ASL(动脉自旋标记)fMRI设计的皮质和皮质下区域的功能成像，将这些心理物理反应的变化与观察到的生理异常相关联。在这项奖学金申请中提出的研究旨在解决对疼痛机制以及慢性疼痛患者的伤害性加工如何发生显着改变的缺乏了解。对支持有害信息时间处理的机制的研究可能有助于和改进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.