Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA.
Metabolism. 2010 Oct;59 Suppl 1:S9-15. doi: 10.1016/j.metabol.2010.07.012.
The relationship between corticosteroids (endogenous and exogenous) and stress is well known, as is the use of steroids as concomitant treatment in pain management during acute inflammation. In the past, steroids have not been considered the first line of treatment in pain management. In this review, we examine new scientific and clinical evidence that demonstrates the direct role that steroids play in the generation and clinical management of chronic pain. We will discuss the new findings demonstrating the fact that steroids and related mediators produce paradoxical effects on pain such as analgesia, hyperalgesia, and even placebo analgesia. In addition, we will examine the physiologic effect of stress, high allostatic load, and idiopathic disease states such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and burnout. The recently observed positive relationship between glutaminergic activity in the insula and clinical pain will be examined in the context of understanding the central role of steroids in chronic pain. The complex role of the hypothalamic-pituitary-adrenal axis in pain will be discussed as well as other heterogeneous forms of chronic pain that involve many components of the central nervous system. Components of the hypothalamic-pituitary-adrenal axis have paradoxical effects on certain types of pain that are dependent on dose and on site (whether peripheral or central) and mode of application. Recent studies on glia have shown that they prolong a state of neuronal hypersensitization in the dorsal root ganglia by releasing growth factors and other substances that act on the immune system. We will discuss the implication of these new findings directly linking pain to steroids, stress, and key higher brain regions in the context of future therapeutic targets.
皮质类固醇（内源性和外源性）与应激之间的关系众所周知，在急性炎症期间使用类固醇作为疼痛管理的伴随治疗也是如此。过去，类固醇并未被认为是疼痛管理的一线治疗药物。在这篇综述中，我们研究了新的科学和临床证据，这些证据表明类固醇在慢性疼痛的产生和临床管理中发挥着直接作用。我们将讨论新的发现，这些发现表明类固醇和相关介质在疼痛中产生矛盾的作用，例如镇痛、痛觉过敏，甚至安慰剂镇痛。此外，我们还将研究应激、高适应负荷以及特发性疾病状态（如慢性疲劳综合征、纤维肌痛、肠易激综合征和倦怠）的生理效应。最近观察到的岛叶谷氨酰胺活性与临床疼痛之间的正相关关系，将在理解类固醇在慢性疼痛中的核心作用的背景下进行研究。还将讨论下丘脑-垂体-肾上腺轴在疼痛中的复杂作用，以及涉及中枢神经系统许多成分的其他异质形式的慢性疼痛。下丘脑-垂体-肾上腺轴的成分对某些类型的疼痛具有矛盾的作用，这些作用取决于剂量和部位（外周或中枢）以及应用方式。最近关于神经胶质的研究表明，它们通过释放作用于免疫系统的生长因子和其他物质，延长背根神经节中神经元超敏状态。我们将讨论这些新发现的意义，这些发现将疼痛与类固醇、应激和关键的高级大脑区域直接联系起来，作为未来治疗靶点的背景。
