Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex

Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex
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氯胺酮通过抑制前扣带皮层的过度活跃来减少啮齿动物疼痛模型的厌恶感

DOI:
10.1038/s41467-018-06295-x
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发表时间:
2018-09
影响因子:
16.6
通讯作者:
Wang Jing
Wang Jing
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhou Haocheng;Zhang Qiaosheng;Martinez Erik;Dale Jahrane;Hu Sile;Zhang Eric;Liu Kevin;Huang Dong;Yang Guang;Chen Zhe;Wang Jing

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已知慢性疼痛会诱导对外周伤害性输入的放大厌恶反应。这种增强的情感反应构成了慢性疼痛综合征(如纤维肌痛)的关键病理特征。然而,作为疼痛处理这一重要方面基础的神经机制仍然知之甚少,阻碍了治疗方法的发展。在这里,我们表明,一个单一剂量的氯胺酮可以产生持久的减少在啮齿动物慢性疼痛模型中的有害刺激的厌恶反应,其抗伤害性作用终止后很长时间。此外,我们证明了这种抗厌恶的性质是通过长时间抑制前扣带皮层(ACC)神经元的过度活跃来介导的,ACC是一个众所周知的调节疼痛影响的大脑区域。因此,我们的研究结果表明,它是可行的,从感觉疼痛的成分分离的情感,并证明了低剂量氯胺酮是一个重要的治疗慢性疼痛综合征的潜力。
Chronic pain is known to induce an amplified aversive reaction to peripheral nociceptive inputs. This enhanced affective response constitutes a key pathologic feature of chronic pain syndromes such as fibromyalgia. However, the neural mechanisms that underlie this important aspect of pain processing remain poorly understood, hindering the development of treatments. Here, we show that a single dose of ketamine can produce a persistent reduction in the aversive response to noxious stimuli in rodent chronic pain models, long after the termination of its anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive property is mediated by prolonged suppression of the hyperactivity of neurons in the anterior cingulate cortex (ACC), a brain region well known to regulate pain affect. Therefore, our results indicate that it is feasible to dissociate the affective from the sensory component of pain, and demonstrate the potential for low-dose ketamine to be an important therapy for chronic pain syndromes.
DOI: --
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