Lee Michelle, Manders Toby R, Eberle Sarah E, Su Chen, D'amour James, Yang Runtao, Lin Hau Yueh, Deisseroth Karl, Froemke Robert C, Wang Jing
Department of Anesthesiology.
Department of Otolaryngology, Department of Neuroscience & Physiology, New York University School of Medicine, New York, New York 10016, Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York, New York 10016, and.
J Neurosci. 2015 Apr 1;35(13):5247-59. doi: 10.1523/JNEUROSCI.3494-14.2015.
Neural circuits that determine the perception and modulation of pain remain poorly understood. The prefrontal cortex (PFC) provides top-down control of sensory and affective processes. While animal and human imaging studies have shown that the PFC is involved in pain regulation, its exact role in pain states remains incompletely understood. A key output target for the PFC is the nucleus accumbens (NAc), an important component of the reward circuitry. Interestingly, recent human imaging studies suggest that the projection from the PFC to the NAc is altered in chronic pain. The function of this corticostriatal projection in pain states, however, is not known. Here we show that optogenetic activation of the PFC produces strong antinociceptive effects in a rat model (spared nerve injury model) of persistent neuropathic pain. PFC activation also reduces the affective symptoms of pain. Furthermore, we show that this pain-relieving function of the PFC is likely mediated by projections to the NAc. Thus, our results support a novel role for corticostriatal circuitry in pain regulation.
目前人们对决定疼痛感知和调节的神经回路仍知之甚少。前额叶皮质（PFC）对感觉和情感过程进行自上而下的控制。虽然动物和人类成像研究表明PFC参与疼痛调节，但其在疼痛状态下的确切作用仍未完全明确。PFC的一个关键输出靶点是伏隔核（NAc），它是奖赏回路的重要组成部分。有趣的是，最近的人类成像研究表明，在慢性疼痛中，从PFC到NAc的投射会发生改变。然而，这种皮质纹状体投射在疼痛状态下的功能尚不清楚。在这里，我们表明，在大鼠持续性神经性疼痛模型（ spared nerve injury model）中，光遗传学激活PFC会产生强烈的抗伤害感受作用。PFC激活还能减轻疼痛的情感症状。此外，我们表明，PFC的这种止痛功能可能是由其向NAc的投射介导的。因此，我们的结果支持皮质纹状体回路在疼痛调节中的新作用。
