盡管嗎啡廣泛應(yīng)用于臨床治療疼痛，但其鎮(zhèn)痛的脊髓上中樞機(jī)制卻不清楚?，F(xiàn)有研究大多聚焦于嗎啡抑制疼痛后的神經(jīng)活動(dòng)改變,，鮮有研究報(bào)告嗎啡在無痛狀態(tài)下對(duì)中樞神經(jīng)元活動(dòng)的調(diào)節(jié),，而后者恰恰是外科手術(shù)中超前鎮(zhèn)痛的基礎(chǔ),。
所謂超前鎮(zhèn)痛，是指在手術(shù)之前就給予鎮(zhèn)痛藥物,，借以抑制傷害性系統(tǒng)的敏化過程,，較常規(guī)的術(shù)后給藥相比，術(shù)前給藥能夠更有效地緩解術(shù)后疼痛以及減少對(duì)鎮(zhèn)痛藥物的需求,。超前鎮(zhèn)痛的機(jī)制迄今并不清楚,，因此，揭示嗎啡對(duì)丘腦-皮層痛覺神經(jīng)網(wǎng)絡(luò)的靜息態(tài)自發(fā)活動(dòng)的調(diào)節(jié)有助于理解嗎啡超前鎮(zhèn)痛的機(jī)制,。
中國科學(xué)院心理健康重點(diǎn)實(shí)驗(yàn)室羅非研究組圍繞這一問題開展了相關(guān)研究,。該研究以成年大鼠為研究對(duì)象,，采用清醒動(dòng)物單個(gè)神經(jīng)元多通道同步記錄技術(shù),，考察在無痛狀態(tài)下單獨(dú)嗎啡用藥對(duì)疼痛感覺通路(初級(jí)軀體感覺皮層和丘腦腹后外側(cè)核)和情緒通路(前扣帶回和丘腦背內(nèi)側(cè)核)神經(jīng)元自發(fā)活動(dòng)及腦區(qū)之間功能連接的調(diào)節(jié)。結(jié)果顯示,，嗎啡用藥導(dǎo)致1/3所記錄的神經(jīng)元的自發(fā)活動(dòng)發(fā)生改變,。對(duì)于疼痛感覺傳導(dǎo)通路，嗎啡主要產(chǎn)生興奮作用,，而對(duì)于情緒傳導(dǎo)通路,，嗎啡則產(chǎn)生興奮和抑制的雙重作用，即一部分神經(jīng)元的活動(dòng)被興奮,，而另一部分神經(jīng)元的活動(dòng)被抑制,。此外，嗎啡用藥之后,，痛覺神經(jīng)網(wǎng)絡(luò)中的丘腦-皮層區(qū)域的功能連接受到顯著抑制,，表現(xiàn)為神經(jīng)元的交互相關(guān)活動(dòng)明顯減弱。
這些結(jié)果表明,，在靜息狀態(tài)下,，嗎啡對(duì)痛覺神經(jīng)網(wǎng)絡(luò)的調(diào)節(jié)（興奮/抑制并存）有別于疼痛狀態(tài)下（全面抑制）的調(diào)節(jié)模式,，這可能是超前鎮(zhèn)痛效果優(yōu)于實(shí)時(shí)鎮(zhèn)痛的機(jī)制所在。相關(guān)論文已發(fā)表于Neuroscience letters,。（生物谷Bioon.com）
doi:10.1016/j.neulet.2012.07.032
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The effects of morphine on basal neuronal activities in the lateral and medial pain pathways
Yuan-Lin Sua, b, Jin Huangc, Ning Wanga, Jin-Yan Wanga, , , Fei Luo
Numerous studies indicate that morphine suppresses pain-evoked activities in both spinal and supraspinal regions. However, little is known about the effect of morphine on the basal brain activity in the absence of pain. The present study was designed to assess the effects of single-dose morphine on the spontaneous discharge of many simultaneously recorded single units, as well as their functional connections, in the lateral pain pathway, including the primary somatosensory cortex (SI) and ventral posterolateral thalamus (VPL), and medial pain pathway, including the anterior cingulate cortex (ACC) and medial dorsal thalamus (MD), in awake rats. Morphine (5 mg/kg) was administered intraperitoneally before the recording. Naloxone plus morphine and normal saline injections were performed respectively as controls. The results showed that morphine administration produced significant changes in the spontaneous neuronal activity in more than one third of the total recorded neurons, with primary activation in the lateral pathway while both inhibition and activation in the medial pathway. Naloxone pretreatment completely blocked the effects induced by morphine. In addition, the correlated activities between and within both pain pathways was exclusively suppressed after morphine injection. These results suggest that morphine may play different roles in modulating neural activity in normal vs. pain states. Taken together, this is the first study investigating the morphine modulation of spontaneous neuronal activity within parallel pain pathways. It can be helpful for revealing neuronal population coding for the morphine action in the absence of pain, and shed light on the supraspinal mechanisms for preemptive analgesia.
