Why sickness hurts: A central mechanism for pain induced by peripheral inflammation
Why sickness hurts: A central mechanism for pain induced by peripheral inflammation
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DOI：
10.1016/j.bbi.2016.04.001
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发表时间：
2016-10-01
影响因子：
15.1
通讯作者：
Axelsson, J.
中科院分区：
文献类型：
--
作者：
Karshikoff, B.;Jensen, K. B.;Axelsson, J.
低度全身性炎症与慢性疼痛以及抑郁和疲劳等共病有关。我们之前已经表明，女性的疼痛感知和调节比男性更受全身炎症的影响。在这里，我们调查了神经基板的基础上，这些影响使用功能磁共振成像范式以前在临床人群。51名受试者（29名女性）分别注射0.6 ng/kg脂多糖（LPS）或生理盐水诱导外周炎症反应，然后在注射后2 h采用旨在捕获下行疼痛抑制活性的加压疼痛fMRI范式对受试者进行测试，并采集血液进行细胞因子分析。与安慰剂组相比，注射LPS的受试者变得对疼痛更敏感，并且与安慰剂组相比，腹外侧前额叶皮层和喙部（前扣带皮层（rACC））的活动减少导致疼痛敏感性增加;参与下行疼痛调节的区域。LPS组的前岛叶皮层也有更高的活性，这是一个支持情感和内感受性疼痛处理的区域。与男性相比，女性显示出总体上较少的疼痛诱发的rACC活性，这可能使女性对免疫激发的弹性较低，这可能解释了LPS诱导的疼痛敏感性的性别差异。我们的研究结果阐明了受实验性外周炎症影响的疼痛相关脑回路，加强了慢性疼痛疾病中全身炎症和疼痛调节减弱之间的理论联系。结果进一步表明，女性在许多慢性疼痛疾病中占主导地位的可能机制。(C)2016 Elsevier Inc. All rights reserved.
Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women's pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fiftyone participants (29 women) were injected with 0.6 ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response.The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2 h after injection, and blood was sampled for cytokine analysis. The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostra( anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disdrders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders. (C) 2016 Elsevier Inc. All rights reserved.