Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism
Increased basal mechanical pain sensitivity but decreased perceptual wind-up in a human model of relative hypocortisolism
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DOI：
10.1016/j.pain.2010.03.026
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发表时间：
2010-06-01
期刊：
影响因子：
7.4
通讯作者：
Anton, Fernand
中科院分区：
文献类型：
--
作者：
Kuehl, Linn K.;Michaux, Gilles P.;Anton, Fernand
积累的临床数据表明，相对皮质醇减少症可能被视为慢性应激的神经内分泌学相关因素，也可能是一些功能性疼痛综合征的特征。然而，下丘脑-垂体-肾上腺（HPA）轴的失调是否可以直接改变疼痛感知，从而在这些疾病的病理生理学中有因果关系，尚未阐明。为了验证这一假设，我们在N = 20名健康无药物志愿者中进行了一项随机安慰剂对照交叉试验（中位年龄24岁），并分析了甲吡酮诱导的皮质醇减少对定量评估的基础机械疼痛敏感性的影响（1.5-13 m/s冲击刺激），知觉上发条（以1Hz的9 m/s冲击刺激）和由指间蹼挤压引起的疼痛的时间总和（IWP; 10 N压力刺激2分钟）。实验诱导的低皮质醇症显著降低了疼痛检测阈值，并增加了IWP诱导疼痛的时间总和（p <0.05）。后一种效应依赖于皮质醇水平的相对降低，并且似乎依赖于增强的致敏作用，而不仅仅依赖于观察到的基础疼痛敏感性的变化。当皮质醇合成被阻断时，对比的感知上发条减少（p <0.05）。这一结果让人想起动物研究的结果，显示在神经性疼痛模型中糖皮质激素受体拮抗剂逆转NMDA受体活化。我们的研究结果支持HPA轴改变在疼痛慢性化中的潜在因果作用。(C)2010年国际疼痛研究协会。由Elsevier B出版。V.保留所有权利。
Clinical data have accumulated showing that relative hypocortisolism, which may be regarded as a neuroendocrinological correlate of chronic stress, may be a characteristic of some functional pain syndromes. However, it has not been clarified yet whether deregulations of the hypothalamus-pituitary-adrenal (HPA) axis may directly alter pain perception and thus be causally involved in the pathophysiology of these disorders. To test this hypothesis, we performed a randomized placebo-controlled crossover trial in N = 20 healthy drug-free volunteers (median age 24 yrs) and analyzed the effects of metyrapone-induced hypocortisolism on quantitatively assessed basal mechanical pain sensitivity (1.5-13 m/s impact stimuli), perceptual wind-up (9 m/s impact stimuli at 1 Hz) and temporal summation of pain elicited by inter-digital web pinching (IWP; 10 N pressure stimuli for 2 min). Experimentally induced hypocortisolism significantly decreased pain detection thresholds and augmented temporal summation of IWP-induced pain (p < .05). The latter effect was dependent on the relative reduction in cortisol levels, and seemed to rely on a potentiated sensitization and not merely on the observed changes in basal pain sensitivity. Perceptual wind-up by contrast was reduced when cortisol synthesis was blocked (p < .05). This result is reminiscent of findings from animal studies showing a reversal of NMDA receptor activation by glucocorticoid receptor antagonists in neuropathic pain models. Our results speak in favor of a potential causal role of HPA axis alterations in pain chronicity. (C) 2010 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.