Long-term potentiation in the anterior cingulate cortex and chronic pain

Glutamate is the primary excitatory transmitter of sensory transmission and perception in the central nervous system. Painful or noxious stimuli from the periphery ‘teach’ humans and animals to avoid potentially dangerous objects or environments, whereas tissue injury itself causes unnecessary chronic pain that can even last for long periods of time. Conventional pain medicines often fail to control chronic pain. Recent neurobiological studies suggest that synaptic plasticity taking place in sensory pathways, from spinal dorsal horn to cortical areas, contributes to chronic pain. Injuries trigger long-term potentiation of synaptic transmission in the spinal cord dorsal horn and anterior cingulate cortex, and such persistent potentiation does not require continuous neuronal activity from the periphery. At the synaptic level, potentiation of excitatory transmission caused by injuries may be mediated by the enhancement of glutamate release from presynaptic terminals and potentiated postsynaptic responses of AMPA receptors. Preventing, ‘erasing’ or reducing such potentiation may serve as a new mechanism to inhibit chronic pain in patients in the future.     

Chronic pain-induced emotional dysfunction is associated with astrogliosis due to cortical delta-opioid receptor dysfunction

It has been widely recognized that chronic pain could cause physiological changes at supraspinal levels. The delta-opioidergic system is involved in antinociception, emotionality, immune response and neuron-glia communication. In this study, we show that mice with chronic pain exhibit anxiety-like behavior and an increase of astrocytes in the cingulate cortex due to the dysfunction of cortical delta-opioid receptor systems. Using neural stem cells cultured from the mouse embryonic forebrain, astrocyte differentiation was clearly observed following long-term exposure to the selective delta-opioid receptor antagonist, naltrindole. We also found that micro-injection of either activated astrocyte or astrocyte-conditioned medium into the cingulate cortex of mice aggravated the expression of anxiety-like behavior. Our results indicate that the chronic pain process promotes astrogliosis in the cingulate cortex through the dysfunction of cortical delta-opioid receptors. This phenomenon may lead to emotional disorders including aggravated anxiety under chronic pain-like state.     

大鼠脑前扣带皮层(ACC)兴奋性与厌恶情绪的行为-电生理学观察*

目的:探讨激活大鼠ACC脑区的阿片受体降低伤害刺激引起厌恶情绪的作用。方法:将实验大鼠随机分为7组,完全弗氏佐剂(CFA)+生理盐水(NS)组,生理盐水(NS)+生理盐水(NS)组,生理盐水(NS)+μ-阿片受体激动剂([DAla², NMe-Phe⁴, Gly-ol⁵]enkephinlin, DAMGO)组,完全弗氏佐剂(CFA)+ 0.01/0.04/0.2/1 μg/μl DAMGO组(n=6)。实验周期为3 d,第1日测量基础值,第2日预先通过ACC区域给药1 μl,然后将0.08 ml完全弗氏佐剂(CFA)注射到大鼠左后脚掌,第3日观察大鼠的CPA反应、缩足反射潜伏期(PWL)和ACC脑区的电活动。结果:①皮下注射CFA的大鼠,注射前与注射后相比,PWL明显减少(P＜0.05);②在笼具痛侧,CFA组大鼠停留的时间明显少于非痛侧(P＜0.05);③在ACC脑区预先注射0.04/0.2/1 μg/μl DAMGO可明显减弱C-CPA反应(P＜0.05);④在ACC脑区预先注射0.04/0.2/1 μg/μl DAMGO可以降低CFA诱发ACC脑区放电频率的增加(P＜0.05)。结论:激活了大鼠ACC脑区上的μ-阿片受体可以降低伤害性刺激诱发的厌恶情绪的发生。     

扣带回前部内脏伤害感受神经元的生物电活动

为了从神经元水平探讨大脑皮层内脏伤害感受的特性及机制,应用玻璃微电极细胞内电位记录技术,研究18只猫扣带回前部312个神经元的自发生物电活动,及其对电刺激同侧内脏大神经的诱发反应.其中,82个为内脏伤害感受神经元,其自发生物电活动有5种主要形式.根据诱发反应的潜伏期等特性,内脏伤害感受神经元分为特异性内脏伤害感受神经元（76个,92.68％）和非特异性内脏伤害感受神经元（6个,7.32％）.内脏伤害性诱发反应分为兴奋性（65.86％）、抑制性（17.07％）及混合性反应（17.07％）3种.结果提示内脏大神经的传入通路投射到同侧扣带回前部;扣带回前部神经元具有内脏伤害感受作用,存有特异性与非特异性内脏伤害感受神经元,为痛觉特异性学说提供了新的实验依据.     

猫扣带回前部内脏伤害感受神经元的诱发反应

应用玻璃微电极细胞内电位记录技术,观察了２０史猫扣带回前部４６１个神经元对电刺激对侧内脏大神经的诱发反应及其电生理特性,在被观察的神经元中,１７６个为刺激相关神经元。根据诱发反应的特性,将其分为特异性内脏伤害感受神经元（１１４个,６４．７７％）、非特异性内脏伤害感受神经元（３４个,１９．３２％）及非内脏伤害感受神经元（２８个,１５．９１％）。诱发反应分为兴奋性（５９．４６％）、抑制性（２２．３０％     

Influence of claustrum on cortex varies by area,layer, and cell type

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长期睡眠剥夺对小鼠蓝斑核线粒体氧化应激及皮层投射的影响

目的：观察长期睡眠剥夺后小鼠蓝斑核线粒体氧化应激状态的变化以及蓝斑核对前扣带回皮质投射的影响。方法：采用“新环境”法建立睡眠剥夺模型。观察小鼠经过5d睡眠剥夺后蓝斑核线粒体氧化应激调控关键酶Sirtuin亚型3（SIRT3）、线粒体氧化应激标记物热休克蛋白60（HSP60）表达量以及前扣带回皮质酪氨酸羟化酶样投射的变化情况。结果：长期睡眠剥夺后,与对照组比较,模型组小鼠蓝斑核SIRT3的表达量显著下调,同时HSP60的表达量则显著上调。此外,模型组前扣带回皮质酪氨酸羟化酶样投射面积百分比显著降低。结论：长期睡眠剥夺通过降低SIRT3的表达影响蓝斑核线粒体氧化应激水平,可能引起蓝斑核对前扣带回皮质投射的丢失。     

刺激大脑皮层体感Ⅱ区对C类纤维传入诱发体感Ⅰ区电反应的影响

电刺激猫大脑皮层体感Ⅱ区(SⅡ)隐神经投射点对隐神经C类纤维传入引起的体感Ⅰ区(SⅠ)诱发电位(C-CEP)有明显的抑制和易化两种影响。前者使C-CEP幅值降低、潜伏期延长;后者使C-CEP幅值升高、时程延长。抑制影响的持续时间较长,而易化持续时间则较短。弱刺激SⅡ区时,易化程度和出现机率较高;而强刺激时,则抑制程度和出现机率较高。弱刺激SⅡ区浅层时,有抑制和易化两种作用;而刺激深层时则只有抑制作用,同样强度刺激深层的抑制效应比刺激浅层大。提示SⅡ区可能对SⅠ区C-CEP有调制作用。     

NMDA受体参与小鼠的前额扣带回的神经突触传递

谷氨酸性突触是哺乳动物神经系统的主要兴奋性突触。在正常条件下,大多数的突触反应是由谷氨酸的AMPA受体传递的。NMDA受体在静息电位下为镁离子抑制。在被激活时,NMDA受体主要参与突触的可塑性变化。但是,许多NMDA受体拮抗剂在全身或局部注射时能产生行为效应,提示NMDA受体可能参与静息状态的生理功能。此文中,我们在离体的前额扣带回脑片上进行电生理记录,发现NMDA受体参与前额扣带回的突触传递。在重复刺激或近于生理性温度时,NMDA受体传递的反应更为明显。本文直接显示了NMDA受体参与前额扣带回的突触传递,并提示NMDA受体在前额扣带回中起着调节神经元兴奋的重要作用。     

胞内记录猫体感皮层内脏伤害性感受神经元的电生理特性

为了从细胞水平探讨皮层内脏伤害感受的特性及机制,本文应用细胞内电位记录技术,观察了猫体感皮层内脏大神经皮层代表区的８５１个神经元对电刺激内脏大神经的诱发反应及电生理特性。其中４１２个单位为内脏伤害性感受神经元,其自发放电有多种形式,根据诱发反应现象分为特异性和非特异性伤害感受神经元,内脏伤害性诱发反应分为兴奋性反应（５１７％）、抑制性反应（３１３１％）及混合性反应（１７％）三类。在形式上具有潜伏期长、反应形式复杂等特点。实验发现８５个神经元为内脏及肋间神经的会聚反应细胞。部分神经元用神经生物素进行细胞内电泳标记以显示功能细胞所在层次及形态。结果说明皮层体感神经元具有内脏伤害性感受的作用,并从细胞及突触后电反应特点上探讨了内脏痛的感受机制。