PAIN & NEURAL DYSFUNCTION FROM ACUTE HERPES ZOSTER

疼痛

• 批准号: 6499450
• 负责人: MICHAEL C ROWBOTHAM
• 金额: $ 18.93万
• 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/6499450
• 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、神经干炎症和神经元损伤是急性带状疱疹（AHZ 或“带状疱疹”）的特征。 大多数 AHZ 患者都能顺利康复，但少数患者会出现持久的神经性疼痛，即带状疱疹后神经痛 (PHN)。 在纵向研究中，年龄、初始疼痛严重程度和心理社会因素已被确定为 PHN 的危险因素，但神经功能障碍和传入神经阻滞的演变（PHN 慢性神经性疼痛的标志）却很少受到研究。 我们假设带状疱疹后神经痛的发展很大程度上取决于两个因素：1）初始神经损伤的严重程度和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 名具有发生 PHN 高风险的 AHZ 患者。 研究参与者将从 AHZ 发病后 2 周到带状疱疹后 6 个月进行密切随访，此时 PHN 已经形成，不太可能自发缓解。 将在 AHZ 发病后 2 周、1 个月、3 个月和 6 个月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、异常性疼痛严重程度的评级，绘制受损伤、疼痛和异常性疼痛影响的皮肤范围，感觉功能的定量测试以及对辣椒素控制应用的反应。 皮肤神经纤维的损失和可能的恢复将通过对受影响和正常皮肤的轴突标记物 PGP 9.5 进行染色的连续皮肤穿刺活检来记录。 剩余纤维中的异常神经功能将明显表现为异常性疼痛、对机械和热刺激的痛觉过敏以及对辣椒素应用的痛觉过敏。 主要传入伤害感受器功能丧失的迹象将明显表现为无法感知有害热量和辣椒素。 神经功能障碍和神经元丢失作为 PHN 危险因素的重要性将与其他研究中发现的危险因素进行比较。