《卒中后中樞痛》ppt課件

1、卒中后中樞性疼痛（Central post-stroke pain，CPSP）,Introduction,Edinger1于1891年提出中樞性疼痛的概念。1906年，Dejerine 、Roussy2發(fā)表的論文《丘腦綜合征》中對(duì)CPSP進(jìn)行了詳細(xì)描述。,1 Edinger L. Giebt es central antstehender Schmerzen?Dtsch Z Nervenheilk 1891; 1: 262–82.

2、2 Déjerine J, Roussy G. Le syndrome thalamique. Rev Neurol (Paris)1906; 14: 521–32,(1) a thalamic lesion,(2) slight hemiplegia,(3) disturbance of superficial and deep sensibility,(4) hemiataxia and hemiastereogno

3、sia,(5) intolerable pain, and(6) choreoathetoid movements,CPSP現(xiàn)被認(rèn)為是“中樞神經(jīng)系統(tǒng)體感通路上的腦血管性病灶直接后果所導(dǎo)致的疼痛”。主要表現(xiàn)為明確軀體部位的疼痛；局部的感覺缺失(-)和疼痛區(qū)域的過度敏感性(+)體征；排除疼痛傷害、精神因素、周圍神經(jīng)病等造成的疼痛中樞性疼痛可由脊髓丘腦和丘腦皮質(zhì)通路上任何部位病變引起，并非局限于丘腦病變。,1 Edinger L.

4、Giebt es central antstehender Schmerzen?Dtsch Z Nervenheilk 1891; 1: 262–82.2 Déjerine J, Roussy G. Le syndrome thalamique. Rev Neurol (Paris)1906; 14: 521–32,Definition of CPSP,H Klit. Central post-stroke pain: cl

5、inical characteristics,pathophysiology, and management Lancet Neurol. 2009 Sep;8(9):857-68,Locations of stroke producing centralpost-stroke pain,Kumar. Anesth Analg 2009;108:1645–57,1 sensory cortex;2 thalamocortical p

6、rojection of spinothalamic sensations;3 ventral posterolateral nucleus of thalamus;4 mid-brain;5 pons6 and 7 medulla,Stroke lesion and Central Poststrokepain localization,Kumar. Anesth Analg 2009;108:1645–57,丘腦腹后外側(cè)核

7、損害最容易引起偏身痛；幕上病變最易導(dǎo)致肢體痛及銳痛和冷感覺減退；幕下病變最易導(dǎo)致面痛，對(duì)熱感覺減退；,Stroke lesion and Central Poststrokepain localization,Epidemiology of CPSP,多數(shù)報(bào)道1-3范圍廣，1%-12%；年輕人多發(fā)4；男性多見（易患丘腦卒中、Wallenberg Syn等）4卒中后即刻到10年內(nèi)均可以發(fā)生CPSP4；18%的丘腦卒中發(fā)病同時(shí)

8、發(fā)生4；,1Bogousslavsky J. Thalamic infarcts: clinical syndromes, etiology, and prognosis. Neurology 1988; 38: 837–48.2Widar M.Long-term pain conditions after a stroke. J Rehabil Med 2002;34: 165–70.3Bowsher D. Stroke and

9、central poststroke pain in an elderly population. J Pain 2001; 2: 258–61.4Gyanendra Kumar. Central post-stroke pain: Current evidence. J Neurological Sci, 284 (2009) 10–17.,Clinical characteristics of CPSP,與病變大小、損傷側(cè)無顯著相

10、關(guān)性；與部位（ brainstem or thalamus）有一定相關(guān)性；自發(fā)痛與誘發(fā)痛并存（spontaneous or evoked）；疼痛分布范圍可大可小 (the hand, to one side of the body) ；受部位影響感覺的“陰性”與“陽性”體征并存（“negative” and “positive” sensory events）；痛覺超敏（Allodynia）、痛覺過敏（Hyp

11、erpathia）與感覺遲滯（Dysesthesias）并存；卒中后不同時(shí)期均可發(fā)生，90%有客觀感覺異常；,Kumar. Anesth Analg 2009;108:1645–57,Kumar B，et al. Anesth Analg. 2009,May;108(5):1645-57,確診標(biāo)準(zhǔn)與CNS損傷相應(yīng)的軀體部位疼痛;有卒中病史且在卒中發(fā)作時(shí)或發(fā)作后開始疼痛;影像證實(shí)CNS損傷灶，與CNS損傷相應(yīng)的陰性或陽性軀體部位感

12、覺體征;排除其它疼痛原因如傷害感受或周圍神經(jīng)病理性疼痛;,,支持標(biāo)準(zhǔn)與運(yùn)動(dòng)、炎癥或其它組織損傷無關(guān)的疼痛;雖然可有各式各樣的疼痛、但主要為灼痛、冷痛、電擊樣痛、酸痛、壓 痛、蟄刺痛、發(fā)麻;觸或冷可誘發(fā)極度疼痛或感覺遲滯;,Diagnostic criteria for CPSP,H Klit. Central post-stroke pain: clinical characteristics,pathophysiology,

13、and management Lancet Neurol. 2009 Sep;8(9):857-68,評(píng)分,,6個(gè)問題,ID Pain：患者自評(píng)量表,Portenoy R. Curr Med Res Opin 2006;22:1555-1565,Portenoy R. Curr Med Res Opin 2006;22:1555-1565.,Pathophysiology: possible mechanisms,中樞敏化（痛覺過敏和痛

14、覺超敏）脊髓丘腦束功能異常（DTI）中樞性失抑制丘腦病變（投射皮質(zhì)的接力神經(jīng)元和GABA能中間抑制性神經(jīng)元）及網(wǎng)狀神經(jīng)元激活（PET/SPECT顯示丘腦代謝及活動(dòng)下降）,Nicholson. Neurology 2004; 62(Suppl 2): S30-36.,1.Central sensitisation,CNS病灶導(dǎo)致大腦結(jié)構(gòu)、神經(jīng)生化改變，興奮性神經(jīng)遞質(zhì)和炎性介質(zhì)釋放 ，增加神經(jīng)元的興奮性；CPSP的自發(fā)痛可能與丘腦或

15、皮層傳入神經(jīng)阻滯，神經(jīng)元興奮性增加或自發(fā)性放電有關(guān)；脫抑制和易化增強(qiáng)，神經(jīng)元興奮性增加導(dǎo)致中樞敏化，慢性疼痛發(fā)生； 許多藥物通過降低神經(jīng)元興奮性而發(fā)揮止痛效果；,2.Alterations in spinothalamic tract function,脊髓丘腦束是重要的感覺傳導(dǎo)通路；脊髓丘腦束通路受損，痛覺和溫度覺信號(hào)傳導(dǎo)紊亂，發(fā)生CPSP；激光誘發(fā)電位（laser-evoked potentials）可以證實(shí)脊髓丘腦

16、束傳導(dǎo)功能損傷1。但不是所有脊髓丘腦束受損的病例都會(huì)出現(xiàn)疼痛；對(duì)針刺覺和溫度覺的高度敏感性在CPSP的病人中更為常見，提示脊髓丘腦束的高度興奮性和持續(xù)激活與疼痛發(fā)生有關(guān),1Bromm B. Electroencephalogr Clin Neurophysiol 1991 Jul–Aug;80(4):284–91.,3.Disinhibition theories（A-C）,A 脊髓丘腦束（STT）向丘腦后外側(cè)傳入減少，引起丘腦內(nèi)側(cè)

17、失抑制B 脊髓丘腦束的外側(cè)冷信號(hào)損害，導(dǎo)致背內(nèi)側(cè)核向島葉的溫度感覺皮質(zhì)傳入受損，邊緣系統(tǒng)和腦干疼痛調(diào)節(jié)結(jié)構(gòu)失抑制C 快速傳導(dǎo)的外側(cè)傳入投射產(chǎn)生的正常的抑制作用損害，引起慢傳導(dǎo)的多突觸傳遞失抑制D 到丘腦的上行通路失傳入（或興奮性增高），引起丘腦神經(jīng)元興奮性增高E STT的病變導(dǎo)致正常存在于丘腦與皮質(zhì)之間的信號(hào)反饋喪失,H Klit. Central post-stroke pain: clinical character

18、istics,pathophysiology, and management Lancet Neurol. 2009 Sep;8(9):857-68,前扣帶皮層,腹后內(nèi)側(cè)核,臂旁核/中腦導(dǎo)水管周圍灰質(zhì),新脊髓丘腦/脊髓丘腦側(cè)束,島葉,脊髓網(wǎng)狀丘腦/脊髓丘腦內(nèi)側(cè)束,4.Thalamic changes,丘腦部位病變CPSP發(fā)生率更高；痛覺超敏（allodynia）發(fā)生時(shí)， SPECT 、 PET掃描發(fā)現(xiàn)丘腦活動(dòng)增強(qiáng)；在

19、CPSP病人可以記錄到丘腦腹后外側(cè)核神經(jīng)元爆發(fā)性放電；動(dòng)物實(shí)驗(yàn)證實(shí)丘腦外側(cè)核的神經(jīng)元興奮性增加是由于經(jīng)脊髓丘腦束上傳到丘腦的上行通路缺失（Fig.D）失傳入、丘腦部位GABA能神經(jīng)元失抑制、膠質(zhì)細(xì)胞激活等與CPSP有關(guān)；,Management of CPSP,Medical Progress January 2009,神經(jīng)病理性疼痛的新型藥物-普瑞巴林（樂瑞卡）,普瑞巴林多途徑抑制疼痛，療效更優(yōu),MARK STILLMAN, MD

20、.CLEVELAND CLINIC JOURNAL OF MEDICINE 2006;73(8):726-739Ivo W. Tremont-Lukats,et al. Drugs 2000 ; 60 (5)Yuichi Takeuchi et al. Neuropharmacology 2007;53:842-853H.-J. YOU,et al. Neuroscience.2009:1845–1853Stephen P.Hu

21、nt et al. NEUROSCIENCE.NATURE REVIEWS.2010:83-91,普瑞巴林(普瑞巴林)1,3,4,抗驚厥藥(如普瑞巴林)阿片制劑NMDA-受體拮抗劑三環(huán)c/SNRI 抗抑郁劑,局部麻醉藥外用止痛藥抗驚厥藥(如卡馬西平2)三環(huán)c/SNRI 抗抑郁劑阿片制劑,抗驚厥藥(如普瑞巴林)阿片三環(huán)c/SNRI 抗抑郁劑1文拉法辛度洛西汀,,,,普瑞巴林可有效作用于中樞神經(jīng)系統(tǒng),1.Michael

22、 Tuchman, et al. Central Sensitization and CaVα 2 δ Ligands in Chronic Pain Syndromes: Pathologic Processes and Pharmacologic Effect. The Journal of Pain, Vol 11, No 12 (December), 2010: pp 1241-12492. David J. Dooley,

23、et al. Ca2+ channel α2δ ligands: novel modulators of neurotransmission.Trends in Pharmacological Sciences.2006;(28)2: 75-82 3. MARK STILLMAN, et al. Clinical approach to patients with neuropathic pain. ClevelandClinic J

24、ournal Of Medicine.2006;73(8): 726-7394. Mitsuo Tanabe, et al. Pain Relief by Gabapentin and Pregabalin Via Supraspinal Mechanisms After Peripheral Nerve Injury. Journal of Neuroscience Research 86.2008;3258-32645. Yui

25、chi Takeuchi, et al. Pregabalin, S-(+)-3-isobutylgaba, activates the descending noradrenergic system to alleviate neuropathic pain in the mouse partial sciatic nerveligation model. Neuropharmacology.2007; 53: 842-8536.

26、 Victoria Chapman, et al. Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats.Pain.1998; 75: 261-2727. A. H. Dickenson, et al.Anti-convulsants and Anti-depressants.

27、 HEP.2006;177:145-77,卡馬西平等藥物無法很好地治療NeP,Safety and efficacy of pregabalin in patients with central post-stroke pain,PAIN. 152 (2011): 1018–1023,研究目的：評(píng)估對(duì)比安慰劑治療CPSP患者的療效和安全性研究設(shè)計(jì)：一項(xiàng)為期13周，隨機(jī)、雙盲、多中心、安慰劑對(duì)照，平行分組研究。研究人群：納入＞18歲C

28、PSP患者219例，普瑞巴林組150-600mg/d,n=110；安慰劑組，n=109；療效對(duì)比：基線時(shí)平均疼痛強(qiáng)度評(píng)分：6.5 vs 6.3；終點(diǎn)時(shí)平均疼痛強(qiáng)度評(píng)分：4.9 vs 5.0 （p=0.578）與安慰劑相比，顯著降低患者焦慮評(píng)分（p=0.015）；顯著改善患者患者睡眠質(zhì)量、臨床總體印象評(píng)分（p＜0.05）,PAIN. 152 (2011): 1018–1023,Weekly mean pain score,普瑞巴林可

29、以緩解患者疼痛,安全性：普瑞巴林組因不良反應(yīng)而終止治療的發(fā)生率為8.2%，安慰劑組為3.7%；普瑞巴林最常見的不良反應(yīng)為：頭暈、嗜睡、外周水腫及體重增加；結(jié)論：普瑞巴林治療卒中后中樞性疼痛有很好的安全性；與安慰劑相比，普瑞巴林可以顯著改善患者睡眠質(zhì)量、焦慮狀態(tài)，提高患者生活質(zhì)量，是臨床治療CPSP的重要選擇藥物。,PAIN. 152 (2011): 1018–1023,總結(jié),CPSP是腦血管事件后發(fā)生的神經(jīng)病理性疼痛綜合征，主要表現(xiàn)

30、為與腦損傷區(qū)域相對(duì)應(yīng)的軀體部位的疼痛與感覺異常；CPSP特點(diǎn)為自發(fā)痛與誘發(fā)痛并存；機(jī)制有中樞敏化、丘腦改變、去抑制等；阿米替林、普瑞巴林、加巴噴丁為一線治療；普瑞巴林調(diào)控鈣離子通道，抑制中樞敏化，是臨床治療CPSP的重要選擇藥物；,Q ＆ A,Case,劉XX，男，68歲。2013.6.28 因“左側(cè)肢體無力6小時(shí)”就診。既往史：高血壓病史，服用絡(luò)活喜5mg/d;體格檢查：Bp160/90mmHg,神志清，左側(cè)中樞性面舌癱

31、，左側(cè)肢體肌力4級(jí)，左側(cè)Babinski sign（+），左側(cè)偏身針刺覺減退；腦CT：右側(cè)基底節(jié)區(qū)低密度灶；診斷：腦梗死（右側(cè)基底節(jié)區(qū)）,2013.10.14 一周前出現(xiàn)左側(cè)肢體麻木疼痛，脹痛，以左手為主，伴燒灼感，睡眠差，情緒低落。體格檢查： 神志清，對(duì)答切題，左鼻唇溝略淺，左側(cè)肢體肌力4.5級(jí)，肌張力正常，左側(cè)偏身針刺覺減退，左手痛覺過敏。ID Pain量表評(píng)分3分，疼痛視覺模擬評(píng)分（VAS）6分診斷：CPSP,