Department of Pharmacology, Institute of Biological Sciences, UFMG, Belo Horizonte, Brazil.
Pharmacology. 2012;89(1-2):22-8. doi: 10.1159/000335095. Epub 2012 Jan 11.
The aim of the present study was to investigate the mechanisms underlying the endogenous control of nociception at a peripheral level during inflammation. Using a pharmacological approach and the rat paw pressure test, we assessed the effect of an intraplantar injection of naloxone, an opioid receptor antagonist, and bestatin, an aminopeptidase inhibitor, on hyperalgesia induced by carrageenan, which mimics an inflammatory process, or prostaglandin E(2) (PGE(2)), which directly sensitizes nociceptors. Naloxone induced a significant and dose-dependent (25, 50 or 100 μg) increase in carrageenan-induced hyperalgesia, but not PGE(2)-induced hyperalgesia. Bestatin (400 μg/paw) significantly counteracted carrageenan-induced hyperalgesia, inducing an increase in the nociceptive threshold compared to control, but it did not modify hyperalgesia induced by PGE(2) injection into the rat paw. Positive β-endorphin immunoreactivity was increased in paw inflammation induced by carrageenan in comparison with the control group. However, PGE(2) did not significantly alter the immunostained area. These results provide evidence for activation of the endogenous opioidergic system during inflammation and indicate that this system regulates hyperalgesia through a negative feedback mechanism, modulating it at a peripheral level.
本研究旨在探讨炎症过程中外周水平内源性痛觉控制的机制。我们采用药理学方法和大鼠足底压力测试，评估了在角叉菜胶（模拟炎症过程）或前列腺素 E2（PGE2）（直接敏化伤害感受器）诱导的痛觉过敏中，足底注射纳洛酮（阿片受体拮抗剂）和贝斯特atin（氨基肽酶抑制剂）的作用。纳洛酮诱导角叉菜胶诱导的痛觉过敏显著且剂量依赖性增加（25、50 或 100μg），但不增加 PGE2 诱导的痛觉过敏。贝斯特atin（400μg/爪）显著拮抗角叉菜胶诱导的痛觉过敏，与对照组相比，增加了伤害感受阈值，但不改变 PGE2 注射到大鼠爪中引起的痛觉过敏。与对照组相比，角叉菜胶诱导的爪炎症中β-内啡肽免疫反应性增加。然而，PGE2 并没有显著改变免疫染色面积。这些结果为炎症过程中内源性阿片能系统的激活提供了证据，并表明该系统通过负反馈机制调节痛觉过敏，在外周水平上调节痛觉过敏。
