PAIN & NEURAL DYSFUNCTION FROM ACUTE HERPES ZOSTER

疼痛、神经干炎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患者恢复顺利，但少数患者发展为持久的神经病理性疼痛--以带状疱疹后神经痛(PHN)的形式出现。在纵向研究中，年龄、初始疼痛程度和心理社会因素已被确定为PHN的危险因素，但作为PHN慢性神经病理性疼痛的特征的神经功能障碍和去传入的演变，几乎没有得到研究。我们假设带状疱疹后神经痛的发展强烈地依赖于两个因素：1)初始神经损伤的严重程度和2)初始神经损伤的恢复能力。为了验证这一假设，我们将前瞻性跟踪200名AHZ患者，这些患者具有发展为PHN的高风险。研究参与者将被密切跟踪，从AHZ发病后2周到带状疱疹后6个月，这段时间PHN已经很好地建立起来，不太可能自发缓解。疼痛和神经损伤的演变将在AHZ发病后2周、1个月、3个月和6个月进行评估。在研究访问中，评估将包括疼痛强度、情绪、生活质量、疼痛严重程度的评级，绘制皮损、疼痛和疼痛影响皮肤的程度图，感官功能的定量测试，以及对辣椒素受控应用的反应。皮神经纤维的丢失和可能的恢复将通过对病变皮肤和正常皮肤进行轴突标记PGP 9.5染色的一系列皮肤穿孔活检来证明。残留纤维的神经功能异常将明显表现为痛觉过敏，对机械和热刺激的痛敏，以及对辣椒素的应用痛敏。初级传入伤害性感受器功能丧失的迹象将明显表现为无法感知有毒的热量和辣椒素。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.