Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Pain. 2012 Nov;153(11):2204-2209. doi: 10.1016/j.pain.2012.06.030. Epub 2012 Aug 23.
Hypoglycemia is a physiological stress that leads to the release of stress hormones, such as catecholamines and glucocorticoids, and proinflammatory cytokines. These factors, in euglycemic animal models, are associated with stress-induced hyperalgesia. The primary aim of this study was to determine whether experimental hypoglycemia in humans would lead to a hyperalgesic state. In 2 separate 3-day admissions separated by 1 to 3 months, healthy study participants were exposed to two 2-hour euglycemic hyperinsulinemic clamps or two 2-hour hypoglycemic hyperinsulinemic clamps. Thermal quantitative sensory testing and thermal pain assessments were measured the day before and the day after euglycemia or hypoglycemia. In contrast to prior euglycemia exposure, prior hypoglycemia exposure resulted in enhanced pain sensitivity to hot and cold stimuli as well as enhanced temporal summation to repeated heat-pain stimuli. These findings suggest that prior exposure to hypoglycemia causes a state of enhanced pain sensitivity that is consistent with stress-induced hyperalgesia. This human model may provide a framework for hypothesis testing and targeted, mechanism-based pharmacological interventions to delineate the molecular basis of hyperalgesia and pain susceptibility.
低血糖是一种生理应激，会导致应激激素（如儿茶酚胺和糖皮质激素）和促炎细胞因子的释放。在血糖正常的动物模型中，这些因素与应激引起的痛觉过敏有关。本研究的主要目的是确定人类的实验性低血糖是否会导致痛觉过敏状态。在间隔 1 至 3 个月的 2 次 3 天住院期间，健康的研究参与者分别接受了 2 次 2 小时的血糖正常高胰岛素血症钳夹或 2 次 2 小时的低血糖高胰岛素血症钳夹。在血糖正常或低血糖之前和之后的一天测量了热定量感觉测试和热痛评估。与之前的血糖正常暴露相比，之前的低血糖暴露导致对热和冷刺激的疼痛敏感性增强，以及对重复热痛刺激的时间总和增强。这些发现表明，先前的低血糖暴露会导致疼痛敏感性增强，这与应激引起的痛觉过敏一致。这种人体模型可能为假说检验和基于机制的靶向药物干预提供框架，以阐明痛觉过敏和疼痛易感性的分子基础。
