PAIN & NEURAL DYSFUNCTION FROM ACUTE HERPES ZOSTER

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患者恢复平静，但少数发展持久的神经性疼痛-在疱疹后神经痛（PHN）的形式。在纵向研究中，年龄、初始疼痛严重程度和社会心理因素已被确定为PHN的危险因素，但作为PHN慢性神经性疼痛的标志，神经功能障碍和神经传递障碍的演变却很少得到研究。我们假设疱疹后神经痛的发生主要取决于两个因素：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。为了验证这一假设，我们将对200名AHZ患者进行前瞻性随访，这些患者有发展为PHN的高风险。研究参与者将在AHZ发病后2周至带状疱疹后6个月期间密切随访，此时PHN已经建立，不太可能自行消退。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情况。在研究访问中，评估将包括疼痛强度、情绪、生活质量、异位性疼痛严重程度的评分，绘制皮肤病变、疼痛和异位性疼痛的影响程度，感觉功能的定量测试，以及对辣椒素控制应用的反应。皮神经纤维的损失和可能的恢复将通过连续的皮肤穿刺活检来记录，在受影响和正常皮肤中染色轴突标记物PGP 9.5。剩余纤维的异常神经功能将表现为对机械和热刺激的异常痛觉，以及对辣椒素应用的痛觉过敏。初级传入伤害感受器功能丧失的迹象将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。

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.