Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 East 2nd Street, Pomona, CA 91766, USA.
Eur J Pharmacol. 2011 Jan 15;650(2-3):563-7. doi: 10.1016/j.ejphar.2010.10.050. Epub 2010 Oct 31.
Stress is known to elicit pain relief, a phenomenon referred to as stress-induced analgesia. Based on stress parameters, opioid and non-opioid intrinsic pain inhibitory systems can be activated. In the present study, we assessed whether changing the duration of stress would affect the involvement of endogenous opioids in antinociception elicited by swim in warm water (32 °C), known to be opioid-mediated. Using mice lacking beta-endorphin, enkephalins or dynorphins and their respective wild-type littermates, we assessed the role of each opioid peptide in antinociception induced by a short (3 min) vs. long (15 min) swim. Mice were tested for baseline hot plate latency, exposed to swim (3 or 15 min) in warm water (32 °C) and then tested for antinociception at 5, 15 and 30 min. Our results revealed that both swim paradigms induced significant antinociception in wild-type mice. However, the short swim failed to induce antinociception in beta-endorphin-deficient mice, illustrating that beta-endorphin is important in this form of stress-induced antinociception. On the other hand, antinociception elicited by the long swim was only slightly reduced in beta-endorphin-deficient mice despite pretreatment with naloxone, a non-selective opioid receptor antagonist, significantly attenuated the antinociception elicited by the long swim. Nevertheless, a delayed hyperalgesic response developed in mice lacking beta-endorphin following exposure to either swim paradigm. On the other hand, mice lacking enkephalins or dynorphins and their respective wild-type littermates expressed a comparable antinociceptive response and did not exhibit the delayed hyperalgesic response. Together, our results suggest that the endogenous opioid peptide beta-endorphin not only mediates antinociception induced by the short swim but also prevents the delayed hyperalgesic response elicited by either swim paradigm.
压力被认为可以减轻疼痛，这种现象被称为应激镇痛。根据压力参数，阿片类和非阿片类内在的疼痛抑制系统可以被激活。在本研究中，我们评估了改变应激的持续时间是否会影响内源性阿片肽参与温水（32°C）游泳诱导的镇痛，已知这种镇痛是阿片类介导的。使用缺乏β-内啡肽、脑啡肽或强啡肽的小鼠及其各自的野生型同窝仔鼠，我们评估了每种阿片肽肽在 3 分钟和 15 分钟游泳诱导的镇痛中的作用。在热板潜伏期的基础上测试了小鼠，将其暴露在温水（32°C）中游泳（3 或 15 分钟），然后在 5、15 和 30 分钟时测试其镇痛作用。我们的结果表明，两种游泳范式都能诱导野生型小鼠显著的镇痛作用。然而，在β-内啡肽缺陷型小鼠中，短游泳未能诱导镇痛作用，这表明β-内啡肽在这种形式的应激镇痛中是重要的。另一方面，尽管用纳洛酮预处理，但纳洛酮是一种非选择性阿片受体拮抗剂，β-内啡肽缺陷型小鼠长游泳诱导的镇痛作用仅略有减少。尽管如此，在暴露于两种游泳范式后，β-内啡肽缺乏的小鼠会出现延迟性痛觉过敏反应。另一方面，缺乏脑啡肽或强啡肽及其各自的野生型同窝仔鼠表达了类似的镇痛反应，并且没有表现出延迟性痛觉过敏反应。总的来说，我们的结果表明，内源性阿片肽β-内啡肽不仅介导短游泳诱导的镇痛作用，而且还防止两种游泳范式诱导的延迟性痛觉过敏反应。
