疼痛的中樞機(jī)制

疼痛的中樞機(jī)制疼

痛DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.“We

must

all

die.

But

that

I

can

save

him

from

days

of

torture,

that

is

what

I

feel

is

mygreat

and

ever

newprivilege.Pain

is

a

moreterrible

lord

of

mankind

than

even

death

itself.”-AlbertSchweitzerDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

疼痛是與實(shí)際或潛在的組織損傷相關(guān)聯(lián)的不愉快的感覺和情緒體驗(yàn)，或用這類組織損傷的詞匯來描述的主訴癥狀；

無交流能力決不能否認(rèn)一個(gè)個(gè)體正有著痛體驗(yàn)，需要適當(dāng)緩解疼痛治療的可能性；

疼痛既是一種生理感覺，又是對這感覺的一種情感反應(yīng)。國際疼痛研究會（IASP）對疼痛的定義（2001):DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.疼痛的意義DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.n

疼痛是一種警戒信號：表示機(jī)體已經(jīng)發(fā)生組織損傷或預(yù)示即將

遭受損傷，通過神經(jīng)系統(tǒng)的調(diào)節(jié)，引起一系

列防御反應(yīng)，保護(hù)機(jī)體避免傷害。疼痛長期持續(xù)不止，便失去警戒意義，反而對機(jī)體構(gòu)成難以忍受的精神折磨，嚴(yán)重影響學(xué)習(xí)、工作、飲食和睡眠，降低生活

質(zhì)量，產(chǎn)生一種不可忽視的經(jīng)濟(jì)和社會問題。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.疼痛的產(chǎn)生DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.n由一定的刺激（傷害性刺激）作用于外周感受器（傷害性感受器），換能后轉(zhuǎn)變成神經(jīng)沖動(dòng)

（傷害性信息），循相應(yīng)的感覺傳入通路（傷

害性傳入通路）進(jìn)人中樞神經(jīng)系統(tǒng)，經(jīng)脊髓、

腦干、間腦中繼后直到大腦邊緣系統(tǒng)和大腦皮

質(zhì)，通過各級中樞整合后產(chǎn)生疼痛感覺和疼痛

反應(yīng)。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.Anesthesiology,?游離的神經(jīng)末梢?廣泛分布于機(jī)體的皮膚、肌肉、關(guān)節(jié)和內(nèi)臟等不同組織DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.傷害感受器

主要是A

δ和C纖維

沿背根進(jìn)入脊髓背角

再將傷害信息傳向脊髓以上的結(jié)構(gòu)DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.傳入傷害信息DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.軀干、四肢的痛覺通路：

新脊-丘束舊脊-丘束或脊-網(wǎng)-丘束

脊-頸束后索-內(nèi)側(cè)丘系脊髓固有束頭面部的痛覺通路：三叉神經(jīng)三叉丘系DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.內(nèi)臟痛覺通路：

交感神經(jīng)

副交感神經(jīng)脊髓上行通路

脊髓丘腦束DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.痛覺的整合中樞疼痛的中樞機(jī)制DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.n20世紀(jì)60年代n脊髓背角的第II層,被認(rèn)為

是“閘門”所在n當(dāng)粗纖維（A

δ

)傳導(dǎo)時(shí)，

形成閘門關(guān)閉效應(yīng)，而細(xì)纖維（C）傳達(dá)時(shí)，形成閘門開

放效應(yīng)

閘門控制學(xué)說-MelzackandWallDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.PainfibreDescendingfacilitationN

+/PainDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.-N

Sensoryfibre

N

Touch

‘A

β’Descending

inhibition閘門控制學(xué)說NSensation-n根據(jù)這一理論,可利用特定的

(高頻、低強(qiáng)度)

電刺激來興

奮粗的有髓纖維,通過抑制同

一節(jié)段細(xì)纖維的傳入而發(fā)揮

鎮(zhèn)痛作用,構(gòu)成了“經(jīng)皮電刺激

鎮(zhèn)痛”(TENS)

的基本原理。n

另外，SCS療法、McGill疼痛問卷（MPQ）也是根據(jù)閘門

控制理論推出的。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.閘門控制學(xué)說DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

20世紀(jì)70年代

發(fā)現(xiàn)“阿片肽”家族內(nèi)源性痛覺調(diào)制系統(tǒng)

“下行抑制系統(tǒng)”的提出DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.阿片肽與阿片受體DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.下行抑制系統(tǒng)DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.內(nèi)源性痛覺調(diào)制系統(tǒng)針刺鎮(zhèn)痛n

20世紀(jì)80年代n

痛覺過敏n

感覺異常n引發(fā)“超前鎮(zhèn)痛”理論可塑性改變或者中樞敏感化DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

痛覺過敏與感覺異常DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.PainfibreDescendingfacilitation

N

+/N

Ascending

pain

‘C’

+

o—N

-

DescendingSensory

fibre

inhibition--

Touch

‘A

β’PainDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.神經(jīng)重塑NSensationDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

中樞敏感化n

疼痛的分子生物學(xué)研究得

到發(fā)展n

尋找痛靶分子n

進(jìn)行靶向治療

20世紀(jì)90年代-DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.SP/NK-1,BDNF/TrkB,EAAs/NMDA,GABA,PKs,ATP/P2X3,COX-2,

Ca2+

,

etc.DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

SP/NK-1受體

SP/NK-1受體o

Activate

phospholipase

C→→↑Ca++n

PIP2->IP3->ligand-gatedERCa++channelsn

PIP2->Diaglyceride->PKC->voltage-sensCa++o

↑c(diǎn)AMPo

↑c(diǎn)GMPoSlowdepolarization–excitatoryo

Enhanced

responsiveness

of

NMDA

receptorDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

BDNF/TrkB受體n

神經(jīng)營養(yǎng)因子家族中的一員，能夠促進(jìn)神經(jīng)細(xì)

胞生長、分化和再生；n

在脊髓背角中作為神經(jīng)遞質(zhì)和神經(jīng)調(diào)質(zhì)，參與

對傷害性感受的調(diào)節(jié)。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.n

促進(jìn)Ca2+離子內(nèi)流，激活PKC蛋白；n

誘導(dǎo)GABA受體磷酸化，使其興奮抑制作用減弱；n

在脊髓神經(jīng)元敏化中具有關(guān)鍵作用，參與神經(jīng)重塑。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.EAAs/NMDA受體n

ATP是傷害性傳入纖維末梢釋放的神經(jīng)遞質(zhì)；n

P2X3只在背根神經(jīng)節(jié)中在與傷害性感受有關(guān)的小直徑細(xì)胞表達(dá)。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.ATP/P2X3受體表達(dá)IL-1受體的

神經(jīng)細(xì)胞