Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, 77555-1069, USA.
Eur J Neurosci. 2014 Feb;39(3):455-66. doi: 10.1111/ejn.12432.
The medial prefrontal cortex (mPFC) serves executive control functions and forms direct connections with subcortical areas such as the amygdala. Our previous work showed abnormal inhibition of mPFC pyramidal cells and hyperactivity of amygdala output neurons in an arthritis pain model. To restore mPFC activity and hence control pain-related amygdala hyperactivity this study focused on CB1 and mGluR5 receptors, which are important modulators of cortical functions. Extracellular single-unit recordings of infralimbic mPFC pyramidal cells and of amygdala output neurons in the laterocapsular division of the central nucleus (CeLC) were made in anesthetised adult male rats. mPFC neurons were classified as 'excited' or 'inhibited' based on their response to brief innocuous and noxious test stimuli. After arthritis pain induction, background activity and evoked responses of excited neurons and background activity and inhibition of inhibited neurons decreased. Stereotaxic application of an mGluR5-positive allosteric modulator (N-cyclobutyl-6-((3-fluorophenyl)ethynyl) nicotinamide hydrochloride, VU0360172) into the mPFC increased background and evoked activity of excited, but not inhibited, mPFC neurons under normal conditions but not in arthritis. A selective CB1 receptor agonist (arachidonyl-2-chloroethylamide) alone had no effect but restored the facilitatory effects of VU0360172 in the pain model. Coactivation of CB1 and mGluR5 in the mPFC inhibited the pain-related activity increase of CeLC neurons but had no effect under normal conditions. The data suggest that excited mPFC neurons are inversely linked to amygdala output (CeLC) and that CB1 can increase mGluR5 function in this subset of mPFC neurons to engage cortical control of abnormally enhanced amygdala output in pain.
内侧前额叶皮层（mPFC）执行执行控制功能，并与杏仁核等皮质下区域形成直接连接。我们之前的工作表明，在关节炎疼痛模型中，mPFC 锥体神经元的抑制异常和杏仁核输出神经元的过度活跃。为了恢复 mPFC 的活动，从而控制与疼痛相关的杏仁核过度活跃，本研究集中于 CB1 和 mGluR5 受体，它们是皮质功能的重要调节剂。在麻醉成年雄性大鼠中，对扣带回皮质下区（CeLC）外侧区的 mPFC 锥体神经元和杏仁核输出神经元进行了细胞外单细胞记录。根据它们对短暂无害和有害测试刺激的反应，将 mPFC 神经元分为“兴奋”或“抑制”。在关节炎疼痛诱导后，兴奋神经元的背景活动和诱发反应以及抑制神经元的背景活动和抑制作用降低。立体定向应用 mGluR5 阳性变构调节剂（N-环丁基-6-（（3-氟苯基）乙炔基）烟酰胺盐酸盐，VU0360172）到 mPFC 中，在正常情况下增加了兴奋但不抑制 mPFC 神经元的背景和诱发活动，但在关节炎中则没有。单独使用选择性 CB1 受体激动剂（花生四烯酰基-2-氯乙基酰胺）没有作用，但在疼痛模型中恢复了 VU0360172 的促进作用。在 mPFC 中共同激活 CB1 和 mGluR5 抑制了 CeLC 神经元与疼痛相关的活动增加，但在正常情况下没有作用。这些数据表明，兴奋的 mPFC 神经元与杏仁核输出（CeLC）呈负相关，并且 CB1 可以增加该亚群 mPFC 神经元中的 mGluR5 功能，以参与皮质对疼痛中异常增强的杏仁核输出的控制。
