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”）的标志。 大多数AHZ患者恢复顺利，但少数发展为持久的神经性疼痛-以疱疹后神经痛（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阻滞的演变（PHN慢性神经病理性疼痛的标志）几乎没有得到研究。 我们假设带状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，我们将前瞻性随访200例PHN高风险AHZ患者。 将对研究受试者从AHZ发作后2周至带状疱疹后6个月进行密切随访，此时PHN已充分确立，不太可能自发缓解。 将在AHZ发作后2周、1个月、3个月和6个月评价疼痛和神经损伤的进展。 在研究访视时，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，绘制病变、疼痛和异常性疼痛影响皮肤的程度，感觉功能的定量测试，以及对辣椒素控制应用的反应。 皮肤神经纤维的丢失和可能的恢复将通过受影响和正常皮肤中的轴突标记物PGP 9.5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。 初级传入伤害感受器功能丧失的迹象将是明显的，因为无法感知有害的热量和辣椒素。 神经功能障碍和神经元丢失作为PHN风险因素的重要性将与其他研究中发现的风险因素进行比较。

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.