神經(jīng)病理性疼痛的概念與診斷-李焰生

神經(jīng)病理性疼痛的概念與診斷上海交通大學(xué)醫(yī)學(xué)院附屬仁濟(jì)醫(yī)院神經(jīng)科李焰生疼痛的解剖和生理傷害性感受器溫度,機(jī)械,化學(xué)Aσ

和C纖維

脊髓后角1,2,5層對側(cè)脊髓丘腦束丘腦VPL核感覺皮質(zhì)邊緣系統(tǒng)

腦干導(dǎo)水管周圍灰質(zhì)藍(lán)斑5-HT NA參與神經(jīng)病理性疼痛的神經(jīng)纖維DworkinClinJPain.2002;18:343-349Rajaetal.inWallPD,MelzackR(Eds).Textbookofpain.4thEd.1999.;11-57神經(jīng)病理性疼痛的定義IASP

由或認(rèn)為是由周圍或中樞神經(jīng)系統(tǒng)障礙所導(dǎo)致的疼痛由神經(jīng)系統(tǒng)原發(fā)性/繼發(fā)性損害或功能障礙或一過性紊亂所引起或?qū)е碌奶弁赐x詞神經(jīng)病性痛，神經(jīng)病變性痛，神經(jīng)性疼痛，神經(jīng)源性疼痛，等等不同于神經(jīng)痛（neuralgia）NEUROLOGY2008;70:1630-1635Neuropathicpain：RedefinitionandagradingsystemforclinicalandresearchpurposesR.-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,PhDandJ.Serra,MDPainusuallyresultsfromactivationofnociceptiveafferents

byactuallyorpotentiallytissue-damagingstimuli.Painmay

alsoarisebyactivitygeneratedwithinthenervoussystemwithout

adequatestimulationofitsperipheralsensoryendings.For

thistypeofpain,theInternationalAssociationfortheStudy

ofPainintroducedthetermneuropathicpain,definedas“pain

initiatedorcausedbyaprimarylesionordysfunctioninthe

nervoussystem.”Whilethisdefinitionhasbeenusefulindistinguishing

somecharacteristicsofneuropathicandnociceptivetypesof

pain,itlacksdefinedboundaries.Sincethesensitivityof

thenociceptivesystemismodulatedbyitsadequateactivation

(e.g.,bycentralsensitization),ithasbeendifficulttodistinguish

neuropathicdysfunctionfromphysiologicneuroplasticity.We

presentamoreprecisedefinitiondevelopedbyagroupofexperts

fromtheneurologicandpaincommunity:painarisingasadirect

consequenceofalesionordiseaseaffectingthesomatosensory

system.Thisreviseddefinitionfitsintothenosologyofneurologic

disorders.Thereferencetothesomatosensorysystemwasderived

fromawiderangeofneuropathicpainconditionsrangingfrom

painfulneuropathytocentralpoststrokepain.Becauseofthe

lackofaspecificdiagnostictoolforneuropathicpain,agrading

systemofdefinite,probable,andpossibleneuropathicpain

isproposed.Thegradepossiblecanonlyberegardedasaworking

hypothesis,whichdoesnotexcludebutdoesnotdiagnoseneuropathic

pain.Thegradesprobableanddefiniterequireconfirmatory

evidencefromaneurologicexamination.Thisgradingsystem

isproposedforclinicalandresearchpurposespainarisingasadirect

consequenceofalesionordiseaseaffectingthesomatosensory

system.疼痛的病理生理神經(jīng)病理性痛疼痛來自于周圍或中樞傷害性感覺結(jié)構(gòu)的異常傷害性痛組織損傷后疼痛完整的周圍和中樞傷害性感覺結(jié)構(gòu)慢性疼痛如炎癥、關(guān)節(jié)炎如DPN、三叉神經(jīng)痛、卒中后疼痛、PHN

混合性痛坐骨神經(jīng)痛，腫瘤痛

burning,pinsandneedles,prickling stabbing hyperalgesia allodynia

touchsensation

painsensation

positionsensation

vibrationsensation

cold/warm

中樞敏感化

周圍敏感化

CNSPNS

CNS“正?！眰π愿惺芷髡鬟f

中樞重組異常傷害性感受器PNSPappagalloM.2001.病理狀態(tài)神經(jīng)病理性疼痛傷害性痛生理狀態(tài)病理生理周圍機(jī)制

周圍神經(jīng)損傷

1.由于神經(jīng)元自發(fā)活動(dòng)、激活閾值下降和對刺激的反應(yīng)增強(qiáng)導(dǎo)致敏感化2.沿神經(jīng)形成表位神經(jīng)元起搏點(diǎn)和納離子通道及電壓門控鈣離子通道表達(dá)增加3.相鄰脫髓鞘軸索產(chǎn)生異常電聯(lián)系通道、神經(jīng)元興奮性增高病理生理神經(jīng)病理性痛可能涉及的生理生化改變

門控學(xué)說Wall&Melzack1965中間神經(jīng)元由A-beta纖維激活起門控作用，抑制由C纖維向高級中樞的疼痛傳入搓揉損害周圍皮膚可減輕疼痛.經(jīng)皮電神經(jīng)刺激(TENS).后柱刺激.針灸

centralperipheralMechanicalhyperalgesiaisduetospinalsensitizationEctopicdischargesPar/dys?sthesias(sodiumchannel)DecreasedcentralinhibitionSpinalhyperexcitability/sensitizationallodynia/mech.hyperalgesia(glutamate)Peripheralsensitizationofnociceptors(inflammatorysubstances)涉及持續(xù)神經(jīng)病理性痛的可能機(jī)制腦脊髓周圍神經(jīng)交感神經(jīng)通道改變分子改變基因表達(dá)改變接受場改變通道改變（鈉）分子改變后角失神經(jīng)后超敏基因表達(dá)改變接受場改變異位發(fā)放（鈉通道異常聚集）機(jī)械敏感假突觸交連（A

）假突觸交連中樞性抑制降低正常神經(jīng)沖動(dòng)的中樞處理過程改變（放大和持續(xù)）國際疼痛研究協(xié)會(huì)的定義(2002)神經(jīng)病理性感覺異常感覺異常神經(jīng)病理性疼痛診斷DN4問卷出現(xiàn)4個(gè)或4個(gè)以上情況即可診斷

燒灼痛 電擊樣 痛性發(fā)冷蟻?zhàn)? 針刺 麻木癢 觸覺減退 針刺覺減退觸覺感痛

BouhassiraD,AttalN,AlchaarHetal.Pain2005;114:29–36.83%敏感性,90%特異性電生理NCV：確定神經(jīng)病變部位了解病變性質(zhì)：軸索、脫髓鞘、小纖維或混合性病變

化驗(yàn)檢查診斷：全血細(xì)胞、常規(guī)生化、血糖、甲狀腺功能、葉酸、B12自身免疫蛋白電泳，冷凝蛋白、單克隆Ig重金屬ASAAnti-HUCSF：CIDP、腦膜癌病組織活檢神經(jīng)(隱神經(jīng)）：血管炎性、淀粉樣變性性、結(jié)節(jié)病性等皮膚：評估真皮的無髓纖維密度神經(jīng)病理性痛診斷分級流程主訴疼痛可能的神經(jīng)解剖分布的疼痛，及病史提示相關(guān)疾病或病變不像是非是可能神經(jīng)病理性痛證實(shí)檢查：A感覺體征，位于病變神經(jīng)分布區(qū)B診斷性檢查證實(shí)有能解釋神經(jīng)病理性痛的疾病或病變無兩者皆有:肯定一項(xiàng)符合：很可能伴隨痛性神經(jīng)病的其他表現(xiàn)失眠焦慮抑郁體重下降生命質(zhì)量下降Gilron,I.etal.