Spinally applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis
Spinally applied ketamine or morphine attenuate peripheral inflammation and hyperalgesia in acute and chronic phases of experimental arthritis
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DOI：
10.1016/j.bbi.2009.12.002
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发表时间：
2010-03-01
影响因子：
15.1
通讯作者：
Schaible, Hans-Georg
中科院分区：
文献类型：
--
作者：
Boettger, Michael Karl;Weber, Konstanze;Schaible, Hans-Georg
炎症引起外周和中枢伤害感受神经元的敏化。后者的药理学调节已成功地用于临床疼痛缓解。特别地，广泛使用NMDA谷氨酸受体的抑制剂如氯胺酮和μ-阿片受体的激动剂如吗啡。除了驱动疼痛信号的传播外，还讨论了脊髓机制以调节外周炎症。在此，我们在慢性抗原诱导性关节炎（AIA）模型中验证了鞘内注射氯胺酮或吗啡不仅能减少疼痛相关行为，而且能减弱炎症反应的诱导和维持的假设。6 h后（急性期）评估肿胀和组织病理学变化。在另一组AIA动物中植入鞘内导管，并连续应用物质。在21天的观察期内，对炎症和疼痛相关行为进行了评估。氯胺酮和吗啡显著降低了关节炎的严重程度，表现为关节肿胀减轻，但更有趣的是，在关节炎的急性和慢性阶段，炎性细胞浸润和关节破坏减少。吗啡表现出强烈的抗伤害性作用，在急性期，而新建立的有效剂量氯胺酮在连续应用设计减少痛觉过敏的急性和慢性stage.In结论，这两种化合物表现出抗炎作用，在诱导和维持关节炎时，应用鞘内。因此，这些数据提出了脊髓NMDA受体和阿片受体在免疫介导的炎症的神经元控制中的作用。(C)2009 Elsevier Inc. All rights reserved.
Inflammation causes sensitization of peripheral and central nociceptive neurons. Pharmacological modulation of the latter has successfully been used for clinical pain relief. In particular, inhibitors of the NMDA glutamate receptor such as ketamine and agonists at the mu-opioid receptor such as morphine are broadly used. Besides driving the propagation of pain signals, spinal mechanisms are also discussed to modulate inflammation in the periphery. Here, we tested the hypothesis that intrathecally applied ketamine or morphine not only reduce pain-related behavior, but also attenuate induction and maintenance of the inflammatory response in a model of chronic antigen-induced arthritis (AIA).Ketamine, morphine or vehicle was applied to the spinal cords of anesthesized animals with AIA. Swelling and histopathological changes were assessed after 6 h (acute phase). Intrathecal catheters were implanted in another set of animals with AIA and substances were applied continuously. During the observation period of 21 days, inflammation and pain-related behavior were assessed.Ketamine and morphine significantly reduced arthritis severity as indicated by reduced joint swelling, but even more intriguingly by reduced infiltration with inflammatory cells and joint destruction in the acute and the chronic phase of arthritis. Morphine showed strong antinociceptive effects in the acute phase only, while the newly established effective dose for ketamine in a continuous application design reduced hyperalgesia in the acute and the chronic stage.In conclusion, both compounds exhibit anti-inflammatory effects during induction and maintenance of arthritis when applied intrathecally. These data thus propose a role of spinal NMDA- and opioid-receptors in the neuronal control of immune-mediated inflammation. (C) 2009 Elsevier Inc. All rights reserved.