神经病理性疼痛的概念与诊断李焰生.ppt

1、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

2、 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 gradin

3、g 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 affer

4、ents 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

5、, 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

6、 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

7、 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

8、 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

9、 probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes,pain 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

10、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 h

11、yperalgesia allodynia touch sensation pain sensation position sensation vibration sensation cold / warm ,中枢敏感化,周围敏感化,CNS,PNS,CNS,“正常” 伤害性感受器,正常传递,中枢重组,异常伤害性感受器,PNS,Pappagallo 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

12、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) 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 接受场扩大，抑制性中间神经元死亡(内源调节系统) 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 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