Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi, People's Republic of China.
Department of Anesthesiology, Perioperative Care and Pain Medicine, New York University School of Medicine, New York, NY, USA.
Mol Brain. 2021 Mar 2;14(1):45. doi: 10.1186/s13041-021-00757-y.
The corticostriatal circuit plays an important role in the regulation of reward- and aversion-types of behaviors. Specifically, the projection from the prelimbic cortex (PL) to the nucleus accumbens (NAc) has been shown to regulate sensory and affective aspects of pain in a number of rodent models. Previous studies have shown that enhancement of glutamate signaling through the NAc by AMPAkines, a class of agents that specifically potentiate the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, reduces acute and persistent pain. However, it is not known whether postsynaptic potentiation of the NAc with these agents can achieve the full anti-nociceptive effects of PL activation. Here we compared the impact of AMPAkine treatment in the NAc with optogenetic activation of the PL on pain behaviors in rats. We found that not only does AMPAkine treatment partially reconstitute the PL inhibition of sensory withdrawals, it fully occludes the effect of the PL on reducing the aversive component of pain. These results indicate that the NAc is likely one of the key targets for the PL, especially in the regulation of pain aversion. Furthermore, our results lend support for neuromodulation or pharmacological activation of the corticostriatal circuit as an important analgesic approach.
皮质纹状体回路在调节奖赏和厌恶类型的行为方面起着重要作用。具体来说，已经表明来自前额皮质（PL）到伏隔核（NAc）的投射调节了几种啮齿动物模型中疼痛的感觉和情感方面。先前的研究表明，通过 AMPAkines 增强 NAc 中的谷氨酸信号传递，AMPAkines 是一类专门增强α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体功能的药物，可减轻急性和持续性疼痛。然而，尚不清楚这些药物在 NAc 中产生的突触后增强是否可以实现 PL 激活的全部抗伤害感受作用。在这里，我们比较了 NAc 中的 AMPAkine 治疗与 PL 的光遗传学激活对大鼠疼痛行为的影响。我们发现，AMPAkine 治疗不仅部分重建了 PL 对感觉退缩的抑制作用，而且完全阻断了 PL 对减轻疼痛厌恶成分的作用。这些结果表明 NAc 可能是 PL 的关键靶点之一，尤其是在调节疼痛厌恶方面。此外，我们的结果支持皮质纹状体回路的神经调节或药理学激活作为一种重要的镇痛方法。
