疼痛的中樞機制

疼痛的中樞機制疼

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.

疼痛是與實際或潛在的組織損傷相關聯(lián)的不愉快的感覺和情緒體驗，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一個個體正有著痛體驗，需要適當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。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：表示機體已經(jīng)發(fā)生組織損傷或預示即將

遭受損傷，通過神經(jīng)系統(tǒng)的調節(jié)，引起一系

列防御反應，保護機體避免傷害。疼痛長期持續(xù)不止，便失去警戒意義，反而對機體構成難以忍受的精神折磨，嚴重影響學習、工作、飲食和睡眠，降低生活

質量，產(chǎn)生一種不可忽視的經(jīng)濟和社會問題。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），換能后轉變成神經(jīng)沖動

（傷害性信息），循相應的感覺傳入通路（傷

害性傳入通路）進人中樞神經(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，通過各級中樞整合后產(chǎn)生疼痛感覺和疼痛

反應。DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.Anesthesiology,?游離的神經(jīng)末梢?廣泛分布于機體的皮膚、肌肉、關節(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

沿背根進入脊髓背角

再將傷害信息傳向脊髓以上的結構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制DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.n20世紀60年代n脊髓背角的第II層,被認為

是“閘門”所在n當粗纖維（A

δ

)傳導時，

形成閘門關閉效應，而細纖維（C）傳達時，形成閘門開

放效應

閘門控制學說-MelzackandWallDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.PainfibreDescendingfacilitationN

+/PainDepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.-N

Sensoryfibre

N

Touch

‘A

β’Descending

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

(高頻、低強度)

電刺激來興

奮粗的有髓纖維,通過抑制同

一節(jié)段細纖維的傳入而發(fā)揮

鎮(zhèn)痛作用,構成了“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.閘門控制學說DepartmentofAnesthesiology,

RuiJin

Hospital,ShanghaiSecond

Medical

University.

20世紀70年代

發(fā)現(xiàn)“阿片肽”家族內(nèi)源性痛覺調制系統(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)源性痛覺調制系統(tǒng)針刺鎮(zhèn)痛n

20世紀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

疼痛的分子生物學研究得

到發(fā)展n

尋找痛靶分子n

進行靶向治療

20世紀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

↑cAMPo

↑cGMPoSlowdepolarization–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，能夠促進神經(jīng)細

胞生長、分化和再生；n

在脊髓背角中作為神經(jīng)遞質和神經(jīng)調質，參與

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

RuiJin

Hospital,ShanghaiSecond

Medical

University.n

促進Ca2+離子內(nèi)流，激活PKC蛋白；n

誘導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；n

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

RuiJin

Hospital,ShanghaiSecond

Medical

University.ATP/P2X3受體表達IL-1受體的

神經(jīng)細胞