Department of Neuroscience and Behaviour, Ribeirão Preto School of Medicine, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP, 14049-900, Brazil.
Eur J Pain. 2012 Jul;16(6):803-15. doi: 10.1002/j.1532-2149.2011.00066.x. Epub 2011 Dec 19.
Pain markedly activates the hypothalamic-pituitary-adrenal (HPA) axis and increases plasma corticosterone release interfering significantly with nociceptive behaviour as well as the mechanism of action of analgesic drugs.
AIMS/METHODS: In the present study, we monitored the time course of circulating corticosterone in two mouse strains (C57Bl/6 and Balb/C) under different pain models. In addition, the stress response was investigated following animal handling, intrathecal (i.t.) manipulation and habituation to environmental conditions commonly used in nociceptive experimental assays. We also examined the influence of within-cage order of testing on plasma corticosterone.
Subcutaneous injection of capsaicin precipitated a prompt stress response whereas carrageenan and complete Freund's adjuvant induced an increased corticosterone release around the third hour post-injection. However, carrageenan induced a longer increased corticosterone in C57Bl/6 mice. In partial sciatic nerve ligation, neuropathic pain model corticosterone increased only in the first days whereas mechanical hypersensitivity remained much longer. Animal handling also represents an important stressor whereas the i.t. injection per se does not exacerbate the handling-induced stress response. Moreover, the order of testing animals from the same cage does not interfere with plasma corticosterone levels in the intrathecal procedure. Animal habituation to the testing apparatus also does not reduce the immediate corticosterone increase as compared with non-habituated mice.
Our data indicate that HPA axis activation in acute and chronic pain models is time dependent and may be dissociated from evoked hyperalgesia. Therefore, HPA-axis activation represents an important variable to be considered when designing experimental assays of persistent pain as well as for interpretation of data.
疼痛显著激活下丘脑-垂体-肾上腺（HPA）轴，增加血浆皮质酮释放，显著干扰伤害感受行为和镇痛药物的作用机制。
目的/方法：在本研究中，我们监测了两种小鼠品系（C57Bl/6 和 Balb/C）在不同疼痛模型下循环皮质酮的时间过程。此外，还研究了动物处理、鞘内（i.t.）操作和适应环境条件（常用于疼痛实验检测）后的应激反应。我们还检查了笼内测试顺序对血浆皮质酮的影响。
皮下注射辣椒素引发了迅速的应激反应，而角叉菜胶和完全弗氏佐剂诱导了注射后第 3 小时左右皮质酮释放增加。然而，角叉菜胶在 C57Bl/6 小鼠中引起了更长时间的皮质酮增加。在部分坐骨神经结扎的神经病理性疼痛模型中，皮质酮仅在最初几天增加，而机械性超敏反应持续时间更长。动物处理也是一个重要的应激源，而鞘内注射本身不会加剧处理引起的应激反应。此外，从同一笼中测试动物的顺序不会干扰鞘内程序中的血浆皮质酮水平。与未适应的小鼠相比，动物适应测试设备并不会减少立即的皮质酮增加。
我们的数据表明，HPA 轴在急性和慢性疼痛模型中的激活是时间依赖性的，并且可能与诱发的痛觉过敏分离。因此，HPA 轴激活是设计持续性疼痛实验检测以及解释数据时需要考虑的一个重要变量。
