Differential Sensitization of amygdala neurons to afferent inputs in a model of arthritic pain
Differential Sensitization of amygdala neurons to afferent inputs in a model of arthritic pain
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DOI：
10.1152/jn.00799.2002
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发表时间：
2003-02-01
影响因子：
2.5
通讯作者：
Li, WD
中科院分区：
文献类型：
--
作者：
Neugebauer, V;Li, WD
疼痛与焦虑和抑郁等负面情绪有关。杏仁核在情绪性中起着关键作用，并已被证明在情感性障碍模型中经历了神经可塑性变化。杏仁中央核(CEA)中的许多神经元是由伤害性输入驱动的，但杏仁核在持续性疼痛状态中的作用尚不清楚。这项研究是第一次在延长疼痛的模型中研究CEA神经元的伤害性处理。对41个麻醉大鼠CEA神经元进行细胞外单位记录。记录每个神经元对关节、肌肉和皮肤的短暂机械刺激以及对皮肤热刺激的反应。绘制背景活动、感受野大小和阈值，并构建刺激-反应函数。通过关节内注射高岭土和角叉菜胶，在单膝关节炎形成前和之后重复测量这些参数。来自膝关节兴奋性输入的多感受性杏仁核神经元(n=20)对伤害性刺激的反应比对深部组织机械刺激(n=20)和皮肤机械刺激(n=11)的反应更强烈。在关节炎诱导后，20个MR神经元中有18个对机械刺激和感受野大小的反应增强。这些变化呈双时相变化(早期峰值：1~1.5h；持续平台期：3~4h)。在关节炎状态下，对热刺激的反应没有改变(7个神经元中的7个)，但背景活动(18个神经元中的16个)和电诱发的顺行活动(12个神经元中的11个)增加。伤害性感觉神经元(NS)在关节炎诱导后对机械刺激、热刺激和电刺激的反应无明显变化。第三组神经元在对照条件下对躯体感觉刺激没有反应(noSOM神经元；n=8)，但在关节炎中对机械刺激而不是热刺激产生长时间的反应(8个神经元中有5个)。这些数据表明，持续的疼痛伴随着CEA神经元亚群的反应增强。他们对机械刺激的敏感度，而不是对热刺激性的敏感度，与过度兴奋的非特异性状态相抵触。MR神经元可以在持续疼痛的情况下整合和评估信息。NOSOM神经元的招募增加了杏仁核处理的增益。NS神经元保留了伤害性和非伤害性输入之间的区别。
Pain is associated with negative affect such as anxiety and depression. The amygdala plays a key role in emotionality and has been shown to undergo neuroplastic changes in models of affective disorders. Many neurons in the central nucleus of the amygdala (CeA) are driven by nociceptive inputs, but the role of the amygdala in persistent pain states is not known. This study is the first to address nociceptive processing by CeA neurons in a model of prolonged pain. Extracellular single-unit recordings were made from 41 CeA neurons in anesthetized rats. Each neuron's responses to brief mechanical stimulation of joints, muscles, and skin and to cutaneous thermal stimuli were recorded. Background activity, receptive field size, and threshold were mapped, and stimulus-response functions were constructed. These parameters were measured repeatedly before and after induction of arthritis in one knee by intraarticular injections of kaolin and carrageenan. Multireceptive (MR) amygdala neurons (n = 20) with excitatory input from the knee joint responded more strongly to noxious than to innocuous mechanical stimuli of deep tissue (n = 20) and skin (n = 11). After induction of arthritis, 18 of 20 MR neurons developed enhanced responses to mechanical stimuli and expansion of receptive field size. These changes occurred with a biphasic time course (early peak: 1-1.5 h; persistent plateau phase: after 3-4 h). Responses to thermal stimuli did not change (7 of 7 neurons), but background activity (16 of 18 neurons) and electrically evoked orthodromic activity (11 of 12 neurons) increased in the arthritic state. Nociceptive-specific (NS) neurons (n = 13) showed no changes of their responses to mechanical, thermal, and electrical stimulation after induction of arthritis. A third group of neurons did not respond to somesthetic stimuli under control conditions (noSOM neurons; n = 8) but developed prolonged responses to mechanical, but not thermal, stimuli in arthritis (5 of 8 neurons). These data suggest that prolonged pain is accompanied by enhanced responsiveness of a subset of CeA neurons. Their sensitization to mechanical, but not thermal, stimuli argues against a nonspecific state of hyperexcitability. MR neurons could serve to integrate and evaluate information in the context of prolonged pain. Recruitment of noSOM neurons increases the gain of amygdala processing. NS neurons preserve the distinction between nociceptive and nonnociceptive inputs.