神经病理性疼痛的概念与诊断上海交通大学医学院附属仁济医院神经科 李焰生疼痛的解剖和生理伤害性感受器 温度,机械,化学A 和 C纤维 脊髓后角1,2,5层对侧脊髓丘脑束丘脑VPL核感觉皮质 边缘系统脑 干 导水管周围灰质 蓝斑 5-HTNA参与神经病理性疼痛的神经纤维A 纤维 大直径、有髓、快传导纤维 机械感受，正常由非伤害性刺激（触觉）激活，感觉异常A 纤维 中等直径、有髓、中速传导纤维 正常由伤害性刺激（锐痛）激活。C 纤维 小直径、无髓、慢传导 正常由伤害性刺激激活，负责继发痛。刺痛、持续灼痛神经病理性疼痛的异常感觉可由A、A或C纤维传导Dworkin Clin J Pain. 2002;18:343-349 Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57神经病理性疼痛的定义IASP由或认为是由周围或中枢神经系统障碍所 导致的疼痛由神经系统原发性/继发性损害或功能障 碍或一过性紊乱所引起或导致的疼痛同义词 神经病性痛，神经病变性痛，神经性疼痛，神经源 性疼痛，等等不同于神经痛（neuralgia）NEUROLOGY 2008;70:1630-1635 Neuropathic pain：Redefinition and a grading system for clinical and research purposes R. -D. Treede, MD, T. S. Jensen, MD, PhD, J. N. Campbell, MD, G. Cruccu, MD, J. O. Dostrovsky, PhD, J. W. Griffin, MD, P. Hansson, MD, DMSc, DDS, R. Hughes, MD, T. Nurmikko, MD, PhD and J. Serra, MD Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as “pain initiated or caused by a primary lesion or dysfunction in the nervous system.” While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposespain arising as a direct consequence of a lesion or disease affecting the somatosensory system.疼痛的病理生理伤害性痛 “正常”伤害性感受器和”潜在”伤害性感受器的激活和敏 感;炎性致痛物质(质子，前列腺素,缓激肽,5-HT,组胺，细 胞因子和腺苷等)在脊髓水平增高，NMDA受体激活神经病理性痛 炎症和非炎症机制 神经系统的异位激活 后角水平的痛觉通路重组 中枢神经系统敏感化 C纤维表达肾上腺素受体,产生交感传出活动 (SMP,sympathetically mediated pain )神经病理性痛 疼痛来自于周围或中 枢伤害性感觉结构的 异常伤害性痛 组织损伤后疼痛 完整的周围和中枢 伤害性感觉结构慢性疼痛如炎症、关节炎如DPN、三叉神经痛 、卒中后疼痛、PHN混合性痛坐骨神经痛， 肿瘤痛burning, pins and needles, prickling stabbing hyperalgesia allodyniatouch sensation pain sensation position sensation vibration sensation cold / warm 中枢敏感化 周围敏感化CNSPNSCNS“正常” 伤害性感受器正常传递中枢重组异常伤害性感受器PNSPappagallo M. 2001.病理状态神经病理性疼痛伤害性痛生理状态病理生理周围机制周围神经损伤1. 由于神经元自发活动、激活阈值下降和对刺激的反应增强 导致敏感化 2. 沿神经形成表位神经元起搏点和纳离子通道及电压门控钙 离子通道表达增加 3. 相邻脱髓鞘轴索产生异常电联系通道、神经元兴奋性增高病理生理中枢机制持续痛性刺激导致脊髓敏感化(后角神经元)1.后角神经元自发活动增加, 活动阈值降低，对突触传入 反应增强 2.接受场扩大，抑制性中间神经元死亡(内源调节系统) 3.NMDA受体介导的中枢性敏感化进一步释放兴奋性氨基酸 和神经肽 4.交感纤维芽生入神经瘤、后根和DRG神经病理性痛可能涉及的生理生化改变门控学说Wall 114: 2936.83% 敏感性, 90% 特异性电生理 NCV： 确定神经病变部位 了解病变性质：轴索、脱髓鞘、小纤维或混合 性病变 化验检查 诊断： 全血细胞、常规生化、血糖、甲状腺功能、叶酸 、B12 自身免疫 蛋白电泳，冷凝蛋白、单克隆Ig 重金属 ASA Anti-HU CSF：CIDP、脑膜癌病组织活检 神经(隐神经）：血管炎性、淀粉样变 性性、结节病性等 皮肤：评估真皮的无髓纤维密度 神经病理性痛诊断分级流程主诉疼痛可能的神经解剖分布的疼痛， 及病史提示相关疾病或病变不像是非是可能神经病理性痛证实检查： A 感觉体征，位于病变神经分布区 B 诊断性检查证实有能解释神经病理性痛的疾病或病变无两者皆有: 肯定一项符合： 很可能伴随痛性神经病的其他表现失眠 焦虑 抑郁 体重下降 生命质量下降Gilron, I. et al. CMAJ 2006;175:265-275神经病理性痛治疗流程考虑非药物治疗（如理疗、心理干预）早期选择 封闭治疗以促进康复（如复杂区域疼痛综合症）如是PHN或局灶神经病 可以表面用利多卡因起始一线治疗： 加巴喷丁、普加巴林、TCA、SNRI无效、部分有效或其他诊断无效、不能耐受部分有效转换其他一线药增加其他一线药无效、不能耐受部分有效单用曲马多或阿片类加用曲马多或阿片类转诊、三线药、介入干预等无效、不能耐受谢谢