神经病理性疼痛的概念与诊断李焰生

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,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.4,th,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 2021;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 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,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响增强导致敏感化,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),后角神经元自发活动增加,活动阈值降低，对突触传入反响增强,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&Melzack 1965,中间神经元由,A-beta,纤维激活起门控作用，抑制由,C,纤维向高级中枢的疼痛传入,搓揉损害周围皮肤可减轻疼痛,.,经皮电神经刺激,(TENS).,后柱刺激,.,针灸,central,peripheral,Mechanical hyperalgesia is due to spinal sensitization,Ectopic discharges,Par/dyssthesias,(sodium channel),Decreased central inhibition,Spinal hyperexcitability/sensitization,allodynia/,mech.hyperalgesia,(glutamate),Peripheral sensitization of nociceptors,(inflammatory substances),涉及持续神经病理性痛的可能机制,脑,脊髓,周围神经,交感神经,通道改变,分子改变,基因表达改变,接受场改变,通道改变钠,分子改变,后角失神经后超敏,基因表达改变,接受场改变,异位发放钠通道异常聚集,机械敏感,假突触交连A,假突触交连,中枢性抑制降低,正常神经冲动的中枢处理过程改变放大和持续,国际疼痛研究协会的定义,(2002),Hyperalgesia:对正常致痛刺激引起的疼痛感增强痛觉过敏,Hypoalgesia:对正常致痛刺激引起的疼痛感减弱痛觉减退,Hyperesthesia:对非伤害性刺激的敏感性增强感觉过敏,Hypoesthesia:对非伤害性刺激的敏感性降低感觉减退,Allodynia:正常时非致痛刺激引起的疼痛异常性疼痛,Dysesthesia：感觉异常,Hyperpathia:对伤害性或非伤害性刺激(尤其是反复刺激)的疼痛感受增强痛觉增强,Paraesthesia：异常的非疼痛性的感觉感觉反常,神经病理性感觉异常,烧灼样，穿刺样，电击样；也可为疼痛，搏动样痛或尖刺感,感觉异常:自发,间断,无痛，异常,Allodynia:动态/固定机械性轻划/压迫；温度性非致痛性冷/热,Hyperalgesia:,原发性PNS敏感化：损伤局部针刺痛觉过敏+热痛觉过敏+持续机械性Allodynia压痛 C纤维,继发性CNS敏感化：损伤周围动态机械性Allodynia+冷痛觉过敏,Hyperpathia:对痛性刺激的迟发,爆破性反响,感觉异常,神经病理性疼痛诊断,DN4,问卷,出现,4,个或,4,个以上情况即可诊断,烧灼痛,电击样痛性发冷,蚁走针刺麻木,痒触觉减退针刺觉减退,触觉感痛,Bouhassira D,Attal N,Alchaar H et al.Pain 2005;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 20