疼痛性周围神经病变医学PPT

疼痛性周围神经病变（PPN)的诊疗,周围神经病的定义、分类及临床表现：疼痛性周围神经病的定义：疼痛产生的机制：疼痛性周围神经病的诊断：疼痛性周围神经病的治疗,周围神经病的定义：发生于周围神经系统的疾病。,周围神经病的定义、分类及临床表现,周围神经病的按照受累神经的分布分类：PolyneuropathyRadiculopathy or polyradiculopathyNeuronopathymotor or sensoryMononeuropathyMultiple mononeuropathies (mononeuropathy, or mononeuritis multiplex)Plexopathy (involvement of multiple nerves in a plexus),周围神经病的定义、分类及临床表现,周围神经病的定义、分类及临床表现,周围神经病的病理分类：segmental demyelinationwallerian degenerationaxonal degeneration,周围神经病的按病程分类：急性亚急性慢性,周围神经病的定义、分类及临床表现,周围神经病的病因分类：遗传性：获得性,代谢性：糖尿病、甲状腺、尿毒症营养性：B族维生素中毒性：药物 （如呋喃唑酮、异烟肼、 长春新碱、胺碘酮、氯喹、苯妥因、 甲硝唑等）；毒物、重金属、酒精免疫性：GBS、淀粉样变、血管性、结节病、副蛋白血症感染性：HIV、lyme、麻风外伤和压迫性：嵌压性（腕管综合征、肘关综合征、跗管综合征。）肿瘤相关：直接侵润和副肿瘤隐匿性：特发性痛性感觉神经病,获得性：,周围神经病的临床表现：运动症状：刺激症状（束颤、痉挛等）；抑制表现（肌无力、肌肉萎缩）感觉症状：抑制症状（感觉缺失、感觉减退）；兴奋症状（感觉过敏、感觉过度、感觉异常、感觉倒错、疼痛）反射：减弱或消失，也可不受影响自主神经功能障碍：最常见：少汗及无汗、体位性低血压,周围神经病的定义、分类及临床表现,疼痛的特征,疼痛,自发性,非自发性 (诱发性),纯感觉型 8-17%,疼痛,持续性 间歇性,跳痛 电击样痛 刀割样痛 刺痛 痉挛样痛 啮咬样疼痛 烧灼样痛 酸痛、压迫样痛 触痛 撕裂样痛,神经根病,坐骨神经痛,由远端到整个肢体,疼痛的特点,疼痛的特点,疼痛性周围神经病的定义：,疼痛性周围神经病的定义：,主要表现：神经病理性疼痛 ！,痛性感觉神经病 痛性感觉和运动神经病,发病机制-痛觉传导/调节通路,Adapted from Gottschalk A, Smith DS. Am Fam Physician. 2001;63:1979-84.,脊髓背角,外周感受器,痛觉受上行和下行通路的调节：上行通路：疼痛从外周神经经脊髓背角传入大脑，感觉疼痛；下行通路：来自于大脑的下行传递可以抑制上行疼痛。神经递质如NE、5-HT等对外周传来的上行疼痛的减弱作用即下行抑制作用非常重要,疼痛产生的机制：,痛性小纤维神经病 (painful small fiber neuropathy, SFN),神经病理性疼痛机制,外周敏化,离子通道异常,中枢敏化,伤害性感受神经元对传入信号的敏感性增加外周神经损伤后，受损的细胞和炎性细胞会释放出化学物质可使伤害感受器发生敏化放大其传入的神经信号,脊髓及脊髓以上痛觉相关神经元的兴奋性异常或者突触传递增加上扬现象刺激依懒性中枢致 敏,多种离子通道的异常参与了神经病理性疼痛的发生钙离子通道钠离子通道氯离子通道钾离子通道,上扬现象,刺激,刺激,初级传入神经纤维,后角神经元,C纤维的重复传入性刺激导致后角神经元放电频率进行性增高,刺激依赖性中枢致敏,A 机械感受器,无害刺激,无害刺激,神经损伤：疼痛感受器活动增强，导致中枢致敏,无痛,痛觉,正常： A兴奋不会刺激与痛觉有关的后角神经元,Woolf CJ, Mannion RJ. Lancet 1999;353:1959-1964,A机械感受器,神经病理性疼痛机制,外周敏化,离子通道异常,中枢敏化,伤害性感受神经元对传入信号的敏感性增加外周神经损伤后，受损的细胞和炎性细胞会释放出化学物质可使伤害感受器发生敏化放大其传入的神经信号,脊髓及脊髓以上痛觉相关神经元的兴奋性异常或者突触传递增加上扬现象刺激依懒性中枢致 敏,多种例子通道的异常参与了神经病理性疼痛的发生钠离子通道钙离子通道钾离子通道氯离子通道,疼痛性周围神经病的诊断：临床表现：电生理检查：神经活检：影像学检查：血液学检查：脑脊液检查：,疼痛性周围神经病的诊断：,神经病理性疼痛的诊断,神经传导测定针极肌电图皮肤交感反应（SSR）定量感觉检查（QST）,神经电生理检测,感觉和运动神经 脱髓鞘、轴索变性 非特异性,神经传导检（NCS）,运动神经轴索功能状态 PPN肯定 无需针极EMG,针极EMG,检测C纤维的电生理特点 客观评价自主神经系统功能,皮肤交感反应（SSR）,通过皮肤对冷、热、冷痛、热痛觉的敏感判断A-和C纤维功能,定量感觉检测（QST）,皮肤神经活检 - 诊断SFN的金标准,定量分析表皮内神经纤维密度 (intraepidermal nerve fiber density, IENFD)观察表皮内神经纤维形态,超声：神经嵌压，创伤MRI：神经肥大，神经根压迫，PN肿瘤,影像学,糖代谢相关检查：空腹及餐后2小时；HbA1c；OGTT毒物筛查免疫球蛋白维生素血清抗体,血生化,WBC: 感染性PN或神经根病抗体检测: 某些免疫介导的PN副肿瘤相关抗体,CSF,病因治疗： 糖尿病：控制血糖； 酒精性：B族维生素； 免疫性：免疫制剂 。对症治疗：疼痛的处理！神经病理性疼痛,疼痛性周围神经病的治疗,疼痛的药物治疗,疼痛的药物治疗,常用药物,作用机制,Evidence-based guidelines for the pharmacologic treatment of neuropathic pain,International Association for the Study of Pain (IASP) Neuropathic Pain Special Interest Group (NeuPSIG), American Pain Society; Canadian Pain Society; Finnish Pain Society; Latin American Federation of IASP; Mexican Pain SocietyEuropean Federation of Neurological Societies (EFNS) Canadian Pain,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Stepwise Pharmacologic Management of Neuropathic Pain,Step 1 Assess pain and establish the diagnosis of NP (Dworkin et al., 2003; Cruccu et al., 2004); if uncertain about the diagnosis, refer to a pain specialist or neurologist Establish and treat the cause of NP; if uncertain about availability of treatments addressing NP etiology, refer to appropriate specialist Identify relevant comorbidities (e.g., cardiac, renal, or hepatic disease, depression, gait instability) that might be relieved or exacerbated by NP treatment, or that might require dosage adjustment or additional monitoring of therapy Explain the diagnosis and treatment plan to the patient, and establish realistic expectations,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Step 2 Initiate therapy of the disease causing NP, if applicable Initiate symptom treatment with one or more of the following: Antidepressant medication: either secondary amine TCA (nortriptyline, desipramine) or SSNRI (duloxetine, venlafaxine) Calcium channel 2- ligand: either gabapentin or pregabalin For patients with localized peripheral NP: topical lidocaine used alone or in combination with 1 of the other first-line therapies For patients with acute NP, neuropathic cancer pain, or episodic exacerbations of severe pain, and when prompt pain relief during titration of a first-line medication to an efficacious dosage is required, opioid analgesics or tramadol may be used alone or in combination with 1 of the first-line therapies Evaluate patient for nonpharmacologic treatments, and initiate if appropriate,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Step 3 Reassess pain and health-related quality of life frequently If substantial pain relief (e.g., average pain reduced to NRS 3/10) and tolerable side effects, continue treatment. If partial pain relief (e.g., average pain remains NRS 4/10) after an adequate trial (see Table 3), add 1 of the other first-line medications If no or inadequate pain relief (e.g., 30% reduction) at target dosage after an adequate trial (see Table 3), switch to an alternative first-line medication,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Step 4 If trials of first-line medications alone and in combination fail, consider second-line medications or referral to a pain specialist or multidisciplinary pain center,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,First-line treatment Second-line treatmentThird-line treatment,Grade A recommendation,Grade B recommendation,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,First-line treatment (一线治疗药物),具有去甲肾上腺素及5-羟色胺再摄取抑制剂作用的抗抑郁药钙通道2-配体（加巴喷丁和普瑞巴林）局部使用利多卡因,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Second-line treatment (二线治疗药物),曲马多鸦片类止痛剂 一线治疗 急性NP，由于癌症引起的NP,严重的NP发作性加重时，及当一线药物加量时需要取得疼痛的缓解时。,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Third-line treatment (三线治疗药物),certain antidepressant medications： bupropion（安非他酮）, citalopram, and paroxetinecertain antiepileptic medications： carbamazepine, lamotrigine, oxcarbazepine, topiramate, and valproic acidtopical low concentration capsaicinDextromethorphan 右美沙芬Memantine 美金刚Mexiletine 美西律,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,Alec B. OConnor, et al. The American Journal of Medicine (2009) 122, S22S32,最近的临床试验,Botulinum Toxin 肉毒素： 29 PHN,创伤后或中风后NP， 4、12周，有效 20 DPN12周，有效 117 PHN，12周 无差别：剂量？High-Concentration Capsaicin Patch辣椒辣贴剂： 3个2期临床试验PHN和痛性HIV，8周，有效 2RCTs：结果矛盾 高剂量：局部副作用Lacosamide 拉科酰胺：,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,最近的临床试验,Lacosamide 拉科酰胺： 电压依赖的钠通道 1个2期临床试验、3个3期平行临床试验：有效DPN 第四个3期临床试验：无效选择性的5HT再回收抑制剂：,Robert H. Dworkin, et al. Mayo Clin Proc. March 2010;85(3)(suppl):S3-S14,选择性的5HT再回收抑制剂： DPN: paroxetine 和 citalopr