PAIN & NEURAL DYSFUNCTION FROM ACUTE HERPES ZOSTER

疼痛

• 批准号: 6038725
• 负责人: MICHAEL C ROWBOTHAM
• 金额: $ 11.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6038725
• 关键词: chronic disease /disorder; clinical research; human subject; hyperalgesia; medical complication; nerve injury; nervous system regeneration; nociceptors; pain; quality of life; shingles

Pain, nerve trunk inflammation, and neuronal injury are hallmarks of acute herpes zoster (AHZ or 'shingles'). The majority of patients with AHZ recover uneventfully, but a minority develop enduring neuropathic pain - in the form of post-herpetic neuralgia (PHN). Age, initial pain severity, and psychosocial factors have been established as risk factors for PHN in longitudinal studies, but evolution of neural dysfunction and deafferentation, the hallmarks of the chronic neuropathic pain of PHN, have received little study. We hypothesize that the development of post-herpetic neuralgia strongly depends on two factors: 1) the severity of the initial neural injury and 2) the ability to recover from the initial neural injury. To test this hypothesis, we will prospectively follow 200 patients with AHZ at high risk for development of PHN. Study participants will be followed closely from 2 weeks after the onset of AHZ to 6 months post-zoster, a time when PHN is well established and unlikely to remit spontaneously. Evolution of pain and neural injury will be evaluated at 2 weeks, 1 month, 3 months, and 6 months after the onset of AHZ. At study visits, assessments will include ratings of pain intensity, mood, quality of life, allodynia severity, mapping the extent of skin affected by lesions, pain, and allodynia, quantitative tests of sensory function, and response to controlled applications of capsaicin. Loss and possible recovery of cutaneous nerve fibers will be documented through serial skin punch biopsies stained for the axonal marker PGP 9.5 in affected and normal skin. Abnormal neural function in remaining fibers will be evident as allodynia, hyperalgesia to mechanical and thermal stimuli, and hyperalgesia to capsaicin application. Signs of loss of primary afferent nociceptor function will be evident as inability to perceive noxious heat and capsaicin. The importance of neural dysfunction and neuronal loss as risk factors for PHN will be compared to risk factors found in other studies.

疼痛，神经躯干炎症和神经元损伤是急性疱疹带状疱疹（AHZ或“带状疱疹”）的标志。 大多数AHZ患者毫不动摇地恢复，但少数患者会以遗传后神经痛（PHN）的形式产生持久的神经性疼痛。 在纵向研究中，已经确定了年龄，最初的疼痛严重程度和社会心理因素为PHN的危险因素，但是神经功能障碍和失效的演变是PHN的慢性神经性疼痛的标志，几乎没有得到研究。 我们假设疗程后神经痛的发展在很大程度上取决于两个因素：1）初始神经损伤的严重程度，以及2）从初始神经损伤中恢复的能力。 为了检验这一假设，我们将前瞻性地跟踪200名AHZ患者，具有PHN的高风险。 研究参与者将紧随其后，从AHZ发作后的2周到裁员后6个月，这是PHN确定并且不太可能自发地汇款的时期。 AHz发作后的2周，1个月，3个月和6个月，将评估疼痛和神经损伤的演变。 在研究访问中，评估将包括疼痛强度，情绪，生活质量，异常性严重程度的评分，映射受病变，疼痛和异常性疾病影响的皮肤程度，感觉功能的定量测试以及对辣椒素受控应用的反应。 损失和可能的皮肤神经纤维的恢复将通过轴突标记物PGP 9.5染色的连续皮肤打孔活检记录在受影响和正常皮肤中。 剩余纤维中的神经功能异常将显而易见，因为异常性疾病，机械和热刺激的痛觉过敏，以及对辣椒素施用的痛觉过敏。 一级传入伤害感受器功能丧失的迹象将显而易见，因为无法感知有害的热和辣椒素。 将神经功能障碍和神经元丧失作为PHN的危险因素的重要性与其他研究中发现的危险因素进行比较。