Alterations in Temporal Aspects of Pain Processing and Modulation

疼痛处理和调节的时间方面的改变

• 批准号: 8033163
• 负责人: Katherine Theresa Martucci
• 金额: $ 3.96万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-08 至 2011-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033163
• 关键词: Absence of pain sensation; Acute; Address; Affect; Agonist; Awareness; Blood flow; Body Regions; Capsaicin; Clinical; Clinical Treatment; Clinical assessments; Complex Regional Pain Syndromes; Contralateral; Detection; Diagnostic; Dimensions; Exhibits; Fellowship; Frequencies; Functional Imaging; Functional Magnetic Resonance Imaging; Heating; Hyperalgesia; Hypersensitivity; Individual; Infusion procedures; Intravenous infusion procedures; Investigation; Mediating; Medicine; Modeling; Naloxone; Narcotic Antagonists; Neuraxis; Nociception; Opioid; Opioid Receptor; Pain; Pain management; Patients; Pattern; Perception; Physiological; Posterior Horn Cells; Process; Psychophysiology; Research; Selection for Treatments; Sensory; Sensory Manifestations; Severities; Site; Spin Labels; Stimulus; Symptoms; System; Tactile; Temperature; Testing; Thalamic structure; Up-Regulation; allodynia; base; blood oxygen level dependent; central sensitization; chronic pain; clinical Diagnosis; design; emotional experience; endogenous opioids; experience; falls; healthy volunteer; heat stimulus; improved; insight; midbrain central gray substance; neurophysiology; neurotransmitter release; receptor; remifentanil; response; tool

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.

描述（由申请人提供）：尽管慢性疼痛非常严重且频繁，但目前的医学缺乏用于治疗选择的诊断工具，以持续有效地减轻个体疼痛。痛觉过敏和异常性疼痛的症状有助于临床诊断，然而，敏感性的更细微的时间变化也可能代表重要的诊断终点。疼痛后感觉，即触觉/热刺激结束后很长时间内疼痛的异常持续，经常在慢性疼痛中观察到，并且可能与由于疼痛调节中断而导致的伤害性信息的时间处理改变有关。为了更好地了解伤害感受处理在临床状态下如何暂时改变，心理物理学和功能磁共振成像研究相结合，将检查健康受试者和 CRPS（复杂区域疼痛综合征）患者，以实现以下具体目标： 目标 1：识别伤害感受处理的暂时改变疼痛感知是中枢敏感化的结果。目标 2：确定支持有害刺激的时间处理的神经药理学底物。目标 3：确定慢性疼痛中疼痛感知暂时改变的神经生理学相关性。偏移镇痛是一种可能代表在有害刺激的时间维度处理过程中内源性抗伤害机制的动态参与的现象。评估补偿镇痛和受试者/患者对不同持续时间和缓慢下降速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在中枢敏化状态（辣椒素热敏化和慢性疼痛）和药理学状态下如何改变操纵（阿片类药物激动剂和拮抗剂）。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，使用皮质和皮质下区域的功能成像，将心理物理反应的这些变化与观察到的生理异常联系起来。该奖学金申请中拟议的研究旨在解决对疼痛机制以及慢性疼痛患者的伤害感受处理如何发生显着改变的理解的缺乏。对支持有害信息时间处理的机制的研究可能有助于并改善病理疼痛状态的临床评估和治疗。