Neurosci Lett：罗非等揭示吗啡调节机制

尽管吗啡广泛应用于临床治疗疼痛，但其镇痛的脊髓上中枢机制却不清楚。现有研究大多聚焦于吗啡抑制疼痛后的神经活动改变，鲜有研究报告吗啡在无痛状态下对中枢神经元活动的调节，而后者恰恰是外科手术中超前镇痛的基础。

所谓超前镇痛，是指在手术之前就给予镇痛药物，借以抑制伤害性系统的敏化过程，较常规的术后给药相比，术前给药能够更有效地缓解术后疼痛以及减少对镇痛药物的需求。超前镇痛的机制迄今并不清楚，因此，揭示吗啡对丘脑-皮层痛觉神经网络的静息态自发活动的调节有助于理解吗啡超前镇痛的机制。

中国科学院心理健康重点实验室罗非研究组围绕这一问题开展了相关研究。该研究以成年大鼠为研究对象，采用清醒动物单个神经元多通道同步记录技术，考察在无痛状态下单独吗啡用药对疼痛感觉通路(初级躯体感觉皮层和丘脑腹后外侧核)和情绪通路(前扣带回和丘脑背内侧核)神经元自发活动及脑区之间功能连接的调节。结果显示，吗啡用药导致1/3所记录的神经元的自发活动发生改变。对于疼痛感觉传导通路，吗啡主要产生兴奋作用，而对于情绪传导通路，吗啡则产生兴奋和抑制的双重作用，即一部分神经元的活动被兴奋，而另一部分神经元的活动被抑制。此外，吗啡用药之后，痛觉神经网络中的丘脑-皮层区域的功能连接受到显著抑制，表现为神经元的交互相关活动明显减弱。

这些结果表明，在静息状态下，吗啡对痛觉神经网络的调节（兴奋/抑制并存）有别于疼痛状态下（全面抑制）的调节模式，这可能是超前镇痛效果优于实时镇痛的机制所在。相关论文已发表于Neuroscience letters。

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.