Boettger Michael Karl, Weber Konstanze, Grossmann David, Gajda Mieczyslaw, Bauer Reinhard, Bär Karl-Jürgen, Schulz Steffen, Voss Andreas, Geis Christian, Bräuer Rolf, Schaible Hans-Georg
Institute of Physiology I, University Hospital Jena, Jena, Germany.
Arthritis Rheum. 2010 May;62(5):1308-18. doi: 10.1002/art.27380.
In addition to the sensitization of pain fibers in inflamed tissues, the increased excitability of the spinal cord is an important mechanism of inflammatory pain. Furthermore, spinal neuronal excitability has been suggested to play a role in modulating peripheral inflammation. This study was undertaken to test the hypothesis that spinal actions of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) add significantly to both hyperalgesia and maintenance of peripheral inflammation.
Rats with antigen-induced arthritis (AIA) were treated intrathecally with the TNFalpha-neutralizing compound etanercept continuously during the complete time course of AIA, which was 3 days for the acute phase and 21 days for the chronic phase. During this time, inflammation and pain-related behavior were monitored. Since a role for autonomic control of inflammation was proposed, measures from heart rate time series were obtained in the acute phase. Findings were compared with those in vehicle-treated animals and in animals receiving etanercept intraperitoneally.
Spinally administered etanercept acutely reduced pain-related behavior, attenuated both the development and the maintenance of inflammation, and was superior to systemic administration. Parameters indicating autonomic modulation showed a shift toward a sympathetically dominated state in vehicle-treated animals, which was prevented by intrathecal etanercept.
Our findings indicate that spinal TNFalpha plays an important role in both pain signaling and modulation of peripheral inflammation. Thus, neutralizing this cytokine at the spinal site not only represents a putative therapeutic option for different pain syndromes, but may be directly used to attenuate peripheral inflammation.
除了炎症组织中痛觉纤维的敏化外，脊髓兴奋性增加是炎性疼痛的重要机制。此外，有研究表明脊髓神经元兴奋性在调节外周炎症中发挥作用。本研究旨在验证以下假设：促炎细胞因子肿瘤坏死因子α（TNFα）的脊髓作用显著加重痛觉过敏并维持外周炎症。
在抗原诱导性关节炎（AIA）的整个病程中，对大鼠进行鞘内注射TNFα中和化合物依那西普，AIA急性期为3天，慢性期为21天。在此期间，监测炎症和疼痛相关行为。由于有人提出自主神经对炎症有控制作用，因此在急性期获取心率时间序列的测量值。将结果与接受溶剂处理的动物以及腹腔注射依那西普的动物的结果进行比较。
鞘内注射依那西普可急性减轻疼痛相关行为，减轻炎症的发生和维持，且优于全身给药。表明自主神经调节的参数显示，接受溶剂处理的动物向交感神经主导状态转变，而鞘内注射依那西普可防止这种转变。
我们的研究结果表明，脊髓TNFα在疼痛信号传导和外周炎症调节中均起重要作用。因此，在脊髓部位中和这种细胞因子不仅是不同疼痛综合征的一种潜在治疗选择，而且可直接用于减轻外周炎症。
