[精品]疼痛的中樞機制ppt

1、疼痛的中樞機制疼痛的中樞機制 于布為于布為 教授教授 上海第二醫(yī)科大學(xué)附屬瑞金醫(yī)院上海第二醫(yī)科大學(xué)附屬瑞金醫(yī)院 department of anesthesiology, ruijin hospital, shanghai second medical university. 疼疼 痛痛 department of anesthesiology, ruijin hospital, shanghai second medical university. department of anesthesiology, ruijin hospital, shanghai second medical u

2、niversity. department of anesthesiology, ruijin hospital, shanghai second medical university. department of anesthesiology, ruijin hospital, shanghai second medical university. department of anesthesiology, ruijin hospital, shanghai second medical university. department of anesthesiology, ruijin hos

3、pital, shanghai second medical university. “we must all die. but that i can save him from days of torture, that is what i feel is my great and ever new privilege. pain is a more terrible lord of mankind than even death itself.” -albert schweitzer department of anesthesiology, ruijin hospital, shangh

4、ai second medical university. 國際疼痛研究會（國際疼痛研究會（iaspiasp）對疼痛的定義（）對疼痛的定義（2001):2001): 疼痛是與實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，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(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)。 department of anesthesiology, ruijin hospital, shanghai second medical university. 疼痛的意義疼痛的意義 departm

5、ent of anesthesiology, ruijin hospital, shanghai second medical university. n 疼痛是一種警戒信號：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(yù)示即將表示機體已經(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)，保護機體避免傷害。列防御反應(yīng)，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(gòu)成難以忍疼痛長期持續(xù)不止，便失去警戒意義，反而對機體構(gòu)成難以忍 受的精神折磨，嚴重影響學(xué)習(xí)、工作、飲食和睡眠，降低生活受的精神折磨，嚴重影響學(xué)習(xí)、

6、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)濟和社會問題。質(zhì)量，產(chǎn)生一種不可忽視的經(jīng)濟和社會問題。 department of anesthesiology, ruijin hospital, shanghai second medical university. 疼痛的產(chǎn)生疼痛的產(chǎn)生 department of anesthesiology, ruijin hospital, shanghai second 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 （傷害性信息），循相應(yīng)的感覺傳入通路（傷 害性傳入

7、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(zhì)，通過各級中樞整合后產(chǎn)生疼痛感覺和疼痛 反應(yīng)。 department of anesthesiology, ruijin hospital, shanghai second medical university. department of anesthesiology, ruijin hospital, shanghai second medical university. 傷害感受器傷害感受器 游離的神經(jīng)末梢 廣泛分布于機體的皮膚、肌肉、關(guān)節(jié)和內(nèi)臟等不同組織 department of anesthesiolog

8、y, ruijin hospital, shanghai second medical university. 傳入傷害信息傳入傷害信息 主要是a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(jié)構(gòu) department of anesthesiology, ruijin hospital, shanghai second medical university. department of anesthesiology, ruijin hospital, shanghai second 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

9、 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 內(nèi)臟痛覺通路： 交感神經(jīng) 副交感神經(jīng) 脊髓上行通路脊髓上行通路 脊髓丘腦束 department of anesthesiology, ruijin hospital, shanghai second medical university. 痛覺的整合中樞痛覺的整合中樞 department of anesthesiology, ruijin hospital, shanghai second medical university. 疼痛的中樞機制疼痛的中樞機制 department of anesthesiolo

10、gy, ruijin hospital, shanghai second medical university. 閘門控制學(xué)說閘門控制學(xué)說-melzack and wall 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(dāng)粗纖維（ a ）傳導(dǎo)時， 形成閘門關(guān)閉效應(yīng)，而細纖 維（c）傳達時，形成閘門開 放效應(yīng) department of anesthesiology, ruijin hospital, shanghai second medical university. n n n + - pain fibre sensory fibre ascending pain

11、c descending inhibition pain sensation descending facilitation - n touch a 閘門控制學(xué)說閘門控制學(xué)說 department of anesthesiology, ruijin hospital, shanghai second medical university. 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(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

12、的。 閘門控制學(xué)說閘門控制學(xué)說 department of anesthesiology, ruijin hospital, shanghai second medical university. 內(nèi)源性痛覺調(diào)制系統(tǒng)內(nèi)源性痛覺調(diào)制系統(tǒng) 20世紀70年代 發(fā)現(xiàn) “阿片肽”家族 “下行抑制系統(tǒng)”的提出 department of anesthesiology, ruijin hospital, shanghai second medical university. 阿片肽與阿片受體阿片肽與阿片受體 department of anesthesiology, ruijin hospital, sha

13、nghai second medical university. 下行抑制系統(tǒng)下行抑制系統(tǒng) department of anesthesiology, ruijin hospital, shanghai second medical university. 內(nèi)源性痛覺調(diào)制系統(tǒng)內(nèi)源性痛覺調(diào)制系統(tǒng) 針刺鎮(zhèn)痛 department of anesthesiology, ruijin hospital, shanghai second medical university. 可塑性改變或者中樞敏感化可塑性改變或者中樞敏感化 n20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 depar

14、tment of anesthesiology, ruijin hospital, shanghai second medical university. 痛覺過敏與感覺異常痛覺過敏與感覺異常 department of anesthesiology, ruijin hospital, shanghai second medical university. 神經(jīng)重塑 n n n + - pain fibre sensory fibre ascending pain c descending inhibition pain sensation descending facilitation +

15、n touch a department of anesthesiology, ruijin hospital, shanghai second medical university. 中樞敏感化中樞敏感化 department of anesthesiology, ruijin hospital, shanghai second medical university. 2020世紀世紀9090年代年代 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進行靶向治療 department of anesthesiology, ruijin hospital, shanghai second

16、medical university. sp/nk-1, bdnf/trkb, eaas/nmda, gaba, pks, atp/p2x3 , cox-2, ca2+ , etc. department of anesthesiology, ruijin hospital, shanghai second medical university. sp/nk-1受體 department of anesthesiology, ruijin hospital, shanghai second medical university. sp/nk-1受體 qactivate phospholipas

17、e cca+ npip2-ip3-ligand-gated er ca+ channels npip2-diaglyceride-pkc-voltage-sens ca+ q camp q cgmp qslow depolarization excitatory qenhanced responsiveness of nmda receptor department of anesthesiology, ruijin hospital, shanghai second 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

18、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)。 department of anesthesiology, ruijin hospital, shanghai second medical university. eaas/nmdaeaas/nmda受體受體 n促進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。 department of anesthesiology, ruijin hospital, shanghai second medical university. atp/

19、p2x3 atp/p2x3受體受體 natp是傷害性傳入纖維末梢釋放的神經(jīng)遞質(zhì)； np2x3只在背根神經(jīng)節(jié)中在與傷害性感受有關(guān)的小 直徑細胞表達。 department of anesthesiology, ruijin hospital, shanghai second medical university. cox-2 表達il-1受體的 神經(jīng)細胞結(jié)合可 以分泌cox-2， 使得pge2的水平 增加，作用于突 觸前后，易化突 觸傳遞，提高神 經(jīng)興奮性。 department of anesthesiology, ruijin hospital, shanghai second medica

20、l university. 膠質(zhì)細胞膠質(zhì)細胞 n神經(jīng)調(diào)制、神經(jīng)營養(yǎng)和神經(jīng)免疫； n與痛覺過敏的產(chǎn)生和疼痛持續(xù)狀態(tài)有關(guān)。 神經(jīng)損傷后，可以激活膠質(zhì)細胞，釋放神經(jīng)活性因子，包括疼 痛相關(guān)的活性物質(zhì)，引起一系列的生化和病理反應(yīng)，參與脊髓 疼痛調(diào)制過程，從而導(dǎo)致痛覺改變或痛覺過敏。 department of anesthesiology, ruijin hospital, shanghai second medical university. 結(jié)結(jié) 語語 department of anesthesiology, ruijin hospital, shanghai second medical un

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